Links to Exploration step
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Effect of Mutation Type and Location on Clinical Outcome in 1,013 Probands with Marfan Syndrome or Related Phenotypes and <italic>FBN1</italic> Mutations: An International Study</title><author><name sortKey="Faivre, L" sort="Faivre, L" uniqKey="Faivre L" first="L." last="Faivre">L. Faivre</name></author><author><name sortKey="Collod Beroud, G" sort="Collod Beroud, G" uniqKey="Collod Beroud G" first="G." last="Collod-Beroud">G. Collod-Beroud</name></author><author><name sortKey="Loeys, B L" sort="Loeys, B L" uniqKey="Loeys B" first="B. L." last="Loeys">B. L. Loeys</name></author><author><name sortKey="Child, A" sort="Child, A" uniqKey="Child A" first="A." last="Child">A. Child</name></author><author><name sortKey="Binquet, C" sort="Binquet, C" uniqKey="Binquet C" first="C." last="Binquet">C. Binquet</name></author><author><name sortKey="Gautier, E" sort="Gautier, E" uniqKey="Gautier E" first="E." last="Gautier">E. Gautier</name></author><author><name sortKey="Callewaert, B" sort="Callewaert, B" uniqKey="Callewaert B" first="B." last="Callewaert">B. Callewaert</name></author><author><name sortKey="Arbustini, E" sort="Arbustini, E" uniqKey="Arbustini E" first="E." last="Arbustini">E. Arbustini</name></author><author><name sortKey="Mayer, K" sort="Mayer, K" uniqKey="Mayer K" first="K." last="Mayer">K. Mayer</name></author><author><name sortKey="Arslan Kirchner, M" sort="Arslan Kirchner, M" uniqKey="Arslan Kirchner M" first="M." last="Arslan-Kirchner">M. Arslan-Kirchner</name></author><author><name sortKey="Kiotsekoglou, A" sort="Kiotsekoglou, A" uniqKey="Kiotsekoglou A" first="A." last="Kiotsekoglou">A. Kiotsekoglou</name></author><author><name sortKey="Comeglio, P" sort="Comeglio, P" uniqKey="Comeglio P" first="P." last="Comeglio">P. Comeglio</name></author><author><name sortKey="Marziliano, N" sort="Marziliano, N" uniqKey="Marziliano N" first="N." last="Marziliano">N. Marziliano</name></author><author><name sortKey="Dietz, H C" sort="Dietz, H C" uniqKey="Dietz H" first="H. C." last="Dietz">H. C. Dietz</name></author><author><name sortKey="Halliday, D" sort="Halliday, D" uniqKey="Halliday D" first="D." last="Halliday">D. Halliday</name></author><author><name sortKey="Beroud, C" sort="Beroud, C" uniqKey="Beroud C" first="C." last="Beroud">C. Beroud</name></author><author><name sortKey="Bonithon Kopp, C" sort="Bonithon Kopp, C" uniqKey="Bonithon Kopp C" first="C." last="Bonithon-Kopp">C. Bonithon-Kopp</name></author><author><name sortKey="Claustres, M" sort="Claustres, M" uniqKey="Claustres M" first="M." last="Claustres">M. Claustres</name></author><author><name sortKey="Muti, C" sort="Muti, C" uniqKey="Muti C" first="C." last="Muti">C. Muti</name></author><author><name sortKey="Plauchu, H" sort="Plauchu, H" uniqKey="Plauchu H" first="H." last="Plauchu">H. Plauchu</name></author><author><name sortKey="Robinson, P N" sort="Robinson, P N" uniqKey="Robinson P" first="P. N." last="Robinson">P. N. Robinson</name></author><author><name sortKey="Ades, L C" sort="Ades, L C" uniqKey="Ades L" first="L. C." last="Adès">L. C. Adès</name></author><author><name sortKey="Biggin, A" sort="Biggin, A" uniqKey="Biggin A" first="A." last="Biggin">A. Biggin</name></author><author><name sortKey="Benetts, B" sort="Benetts, B" uniqKey="Benetts B" first="B." last="Benetts">B. Benetts</name></author><author><name sortKey="Brett, M" sort="Brett, M" uniqKey="Brett M" first="M." last="Brett">M. Brett</name></author><author><name sortKey="Holman, K J" sort="Holman, K J" uniqKey="Holman K" first="K. J." last="Holman">K. J. Holman</name></author><author><name sortKey="De Backer, J" sort="De Backer, J" uniqKey="De Backer J" first="J." last="De Backer">J. De Backer</name></author><author><name sortKey="Coucke, P" sort="Coucke, P" uniqKey="Coucke P" first="P." last="Coucke">P. Coucke</name></author><author><name sortKey="Francke, U" sort="Francke, U" uniqKey="Francke U" first="U." last="Francke">U. Francke</name></author><author><name sortKey="De Paepe, A" sort="De Paepe, A" uniqKey="De Paepe A" first="A." last="De Paepe">A. De Paepe</name></author><author><name sortKey="Jondeau, G" sort="Jondeau, G" uniqKey="Jondeau G" first="G." last="Jondeau">G. Jondeau</name></author><author><name sortKey="Boileau, C" sort="Boileau, C" uniqKey="Boileau C" first="C." last="Boileau">C. Boileau</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">17701892</idno><idno type="pmc">1950837</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1950837</idno><idno type="RBID">PMC:1950837</idno><date when="2007">2007</date><idno type="wicri:Area/Pmc/Corpus">000038</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000038</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Effect of Mutation Type and Location on Clinical Outcome in 1,013 Probands with Marfan Syndrome or Related Phenotypes and <italic>FBN1</italic> Mutations: An International Study</title><author><name sortKey="Faivre, L" sort="Faivre, L" uniqKey="Faivre L" first="L." last="Faivre">L. Faivre</name></author><author><name sortKey="Collod Beroud, G" sort="Collod Beroud, G" uniqKey="Collod Beroud G" first="G." last="Collod-Beroud">G. Collod-Beroud</name></author><author><name sortKey="Loeys, B L" sort="Loeys, B L" uniqKey="Loeys B" first="B. L." last="Loeys">B. L. Loeys</name></author><author><name sortKey="Child, A" sort="Child, A" uniqKey="Child A" first="A." last="Child">A. Child</name></author><author><name sortKey="Binquet, C" sort="Binquet, C" uniqKey="Binquet C" first="C." last="Binquet">C. Binquet</name></author><author><name sortKey="Gautier, E" sort="Gautier, E" uniqKey="Gautier E" first="E." last="Gautier">E. Gautier</name></author><author><name sortKey="Callewaert, B" sort="Callewaert, B" uniqKey="Callewaert B" first="B." last="Callewaert">B. Callewaert</name></author><author><name sortKey="Arbustini, E" sort="Arbustini, E" uniqKey="Arbustini E" first="E." last="Arbustini">E. Arbustini</name></author><author><name sortKey="Mayer, K" sort="Mayer, K" uniqKey="Mayer K" first="K." last="Mayer">K. Mayer</name></author><author><name sortKey="Arslan Kirchner, M" sort="Arslan Kirchner, M" uniqKey="Arslan Kirchner M" first="M." last="Arslan-Kirchner">M. Arslan-Kirchner</name></author><author><name sortKey="Kiotsekoglou, A" sort="Kiotsekoglou, A" uniqKey="Kiotsekoglou A" first="A." last="Kiotsekoglou">A. Kiotsekoglou</name></author><author><name sortKey="Comeglio, P" sort="Comeglio, P" uniqKey="Comeglio P" first="P." last="Comeglio">P. Comeglio</name></author><author><name sortKey="Marziliano, N" sort="Marziliano, N" uniqKey="Marziliano N" first="N." last="Marziliano">N. Marziliano</name></author><author><name sortKey="Dietz, H C" sort="Dietz, H C" uniqKey="Dietz H" first="H. C." last="Dietz">H. C. Dietz</name></author><author><name sortKey="Halliday, D" sort="Halliday, D" uniqKey="Halliday D" first="D." last="Halliday">D. Halliday</name></author><author><name sortKey="Beroud, C" sort="Beroud, C" uniqKey="Beroud C" first="C." last="Beroud">C. Beroud</name></author><author><name sortKey="Bonithon Kopp, C" sort="Bonithon Kopp, C" uniqKey="Bonithon Kopp C" first="C." last="Bonithon-Kopp">C. Bonithon-Kopp</name></author><author><name sortKey="Claustres, M" sort="Claustres, M" uniqKey="Claustres M" first="M." last="Claustres">M. Claustres</name></author><author><name sortKey="Muti, C" sort="Muti, C" uniqKey="Muti C" first="C." last="Muti">C. Muti</name></author><author><name sortKey="Plauchu, H" sort="Plauchu, H" uniqKey="Plauchu H" first="H." last="Plauchu">H. Plauchu</name></author><author><name sortKey="Robinson, P N" sort="Robinson, P N" uniqKey="Robinson P" first="P. N." last="Robinson">P. N. Robinson</name></author><author><name sortKey="Ades, L C" sort="Ades, L C" uniqKey="Ades L" first="L. C." last="Adès">L. C. Adès</name></author><author><name sortKey="Biggin, A" sort="Biggin, A" uniqKey="Biggin A" first="A." last="Biggin">A. Biggin</name></author><author><name sortKey="Benetts, B" sort="Benetts, B" uniqKey="Benetts B" first="B." last="Benetts">B. Benetts</name></author><author><name sortKey="Brett, M" sort="Brett, M" uniqKey="Brett M" first="M." last="Brett">M. Brett</name></author><author><name sortKey="Holman, K J" sort="Holman, K J" uniqKey="Holman K" first="K. J." last="Holman">K. J. Holman</name></author><author><name sortKey="De Backer, J" sort="De Backer, J" uniqKey="De Backer J" first="J." last="De Backer">J. De Backer</name></author><author><name sortKey="Coucke, P" sort="Coucke, P" uniqKey="Coucke P" first="P." last="Coucke">P. Coucke</name></author><author><name sortKey="Francke, U" sort="Francke, U" uniqKey="Francke U" first="U." last="Francke">U. Francke</name></author><author><name sortKey="De Paepe, A" sort="De Paepe, A" uniqKey="De Paepe A" first="A." last="De Paepe">A. De Paepe</name></author><author><name sortKey="Jondeau, G" sort="Jondeau, G" uniqKey="Jondeau G" first="G." last="Jondeau">G. Jondeau</name></author><author><name sortKey="Boileau, C" sort="Boileau, C" uniqKey="Boileau C" first="C." last="Boileau">C. Boileau</name></author></analytic><series><title level="j">American Journal of Human Genetics</title><idno type="ISSN">0002-9297</idno><idno type="eISSN">1537-6605</idno><imprint><date when="2007">2007</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Mutations in the fibrillin-1 (<italic>FBN1</italic>) gene cause Marfan syndrome (MFS) and have been associated with a wide range of overlapping phenotypes. Clinical care is complicated by variable age at onset and the wide range of severity of aortic features. The factors that modulate phenotypical severity, both among and within families, remain to be determined. The availability of international <italic>FBN1</italic> mutation Universal Mutation Database (UMD-<italic>FBN1</italic>) has allowed us to perform the largest collaborative study ever reported, to investigate the correlation between the <italic>FBN1</italic> genotype and the nature and severity of the clinical phenotype. A range of qualitative and quantitative clinical parameters (skeletal, cardiovascular, ophthalmologic, skin, pulmonary, and dural) was compared for different classes of mutation (types and locations) in 1,013 probands with a pathogenic <italic>FBN1</italic> mutation. A higher probability of ectopia lentis was found for patients with a missense mutation substituting or producing a cysteine, when compared with other missense mutations. Patients with an <italic>FBN1</italic> premature termination codon had a more severe skeletal and skin phenotype than did patients with an inframe mutation. Mutations in exons 24–32 were associated with a more severe and complete phenotype, including younger age at diagnosis of type I fibrillinopathy and higher probability of developing ectopia lentis, ascending aortic dilatation, aortic surgery, mitral valve abnormalities, scoliosis, and shorter survival; the majority of these results were replicated even when cases of neonatal MFS were excluded. These correlations, found between different mutation types and clinical manifestations, might be explained by different underlying genetic mechanisms (dominant negative versus haploinsufficiency) and by consideration of the two main physiological functions of fibrillin-1 (structural versus mediator of TGFβ signalling). Exon 24–32 mutations define a high-risk group for cardiac manifestations associated with severe prognosis at all ages.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Am J Hum Genet</journal-id><journal-id journal-id-type="publisher-id">AJHG</journal-id><journal-title>American Journal of Human Genetics</journal-title><issn pub-type="ppub">0002-9297</issn><issn pub-type="epub">1537-6605</issn><publisher><publisher-name>The American Society of Human Genetics</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">17701892</article-id><article-id pub-id-type="pmc">1950837</article-id><article-id pub-id-type="publisher-id">44568</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Effect of Mutation Type and Location on Clinical Outcome in 1,013 Probands with Marfan Syndrome or Related Phenotypes and <italic>FBN1</italic> Mutations: An International Study</article-title><alt-title>Genotype-Phenotype Correlation in the <italic>FBN1</italic> Gene</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Faivre</surname><given-names>L. </given-names></name></contrib><contrib contrib-type="author"><name><surname>Collod-Beroud</surname><given-names>G. </given-names></name></contrib><contrib contrib-type="author"><name><surname>Loeys</surname><given-names>B. L. </given-names></name></contrib><contrib contrib-type="author"><name><surname>Child</surname><given-names>A. </given-names></name></contrib><contrib contrib-type="author"><name><surname>Binquet</surname><given-names>C. </given-names></name></contrib><contrib contrib-type="author"><name><surname>Gautier</surname><given-names>E. </given-names></name></contrib><contrib contrib-type="author"><name><surname>Callewaert</surname><given-names>B. </given-names></name></contrib><contrib contrib-type="author"><name><surname>Arbustini</surname><given-names>E. </given-names></name></contrib><contrib contrib-type="author"><name><surname>Mayer</surname><given-names>K. </given-names></name></contrib><contrib contrib-type="author"><name><surname>Arslan-Kirchner</surname><given-names>M. </given-names></name></contrib><contrib contrib-type="author"><name><surname>Kiotsekoglou</surname><given-names>A. </given-names></name></contrib><contrib contrib-type="author"><name><surname>Comeglio</surname><given-names>P. </given-names></name></contrib><contrib contrib-type="author"><name><surname>Marziliano</surname><given-names>N. </given-names></name></contrib><contrib contrib-type="author"><name><surname>Dietz</surname><given-names>H. C. </given-names></name></contrib><contrib contrib-type="author"><name><surname>Halliday</surname><given-names>D. </given-names></name></contrib><contrib contrib-type="author"><name><surname>Beroud</surname><given-names>C. </given-names></name></contrib><contrib contrib-type="author"><name><surname>Bonithon-Kopp</surname><given-names>C. </given-names></name></contrib><contrib contrib-type="author"><name><surname>Claustres</surname><given-names>M. </given-names></name></contrib><contrib contrib-type="author"><name><surname>Muti</surname><given-names>C. </given-names></name></contrib><contrib contrib-type="author"><name><surname>Plauchu</surname><given-names>H. </given-names></name></contrib><contrib contrib-type="author"><name><surname>Robinson</surname><given-names>P. N. </given-names></name></contrib><contrib contrib-type="author"><name><surname>Adès</surname><given-names>L. C. </given-names></name></contrib><contrib contrib-type="author"><name><surname>Biggin</surname><given-names>A. </given-names></name></contrib><contrib contrib-type="author"><name><surname>Benetts</surname><given-names>B. </given-names></name></contrib><contrib contrib-type="author"><name><surname>Brett</surname><given-names>M. </given-names></name></contrib><contrib contrib-type="author"><name><surname>Holman</surname><given-names>K. J. </given-names></name></contrib><contrib contrib-type="author"><name><surname>De Backer</surname><given-names>J. </given-names></name></contrib><contrib contrib-type="author"><name><surname>Coucke</surname><given-names>P. </given-names></name></contrib><contrib contrib-type="author"><name><surname>Francke</surname><given-names>U. </given-names></name></contrib><contrib contrib-type="author"><name><surname>De Paepe</surname><given-names>A. </given-names></name></contrib><contrib contrib-type="author"><name><surname>Jondeau</surname><given-names>G. </given-names></name></contrib><contrib contrib-type="author"><name><surname>Boileau</surname><given-names>C. </given-names></name></contrib></contrib-group><aff id="N0xfd5afd0N0x5988558">From the Centre de Génétique, Centre Hospitalier Universitaire (CHU) (L.F.), Centre d’Investigation Clinique–Épidémiologie Clinique/Essais Cliniques, (L.F.; C. Binquet; E.G.; C.B.-K.), and INSERM CIE1 (C. Binquet; E.G.; C.B.-K.), Dijon, France; INSERM U827 (G.C.-B.; C. Beroud; M.C.), University of Montpellier I (G.C.-B.; C. Beroud; M.C.), and CHU Montpellier, Laboratoire de Génétique Moléculaire, Hôpital Arnault de Villeneuve (C. Beroud; M.C.), Montpellier, France; Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium (B.L.L.; B.C.; J.D.B.; P. Coucke; A.D.P.); Institute of Genetic Medicine and the Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore (B.L.L.; H.C.D.); Department of Cardiological Sciences, St. George’s Hospital, London (A.C.; A.K.; P. Comeglio); Centre for Inherited Cardiovascular Diseases, Foundation IRCCS Policlinico San Matteo, Pavia, Italy (E.A.; N.M.); Center for Human Genetics and Laboratory Medicine, Martinsried, Germany (K.M.); Institute of Human Genetics, Hannover Medical School, Hannover (M.A.-K.); Department of Biochemistry, University of Oxford, Oxford, United Kingdom (D.H.); Consultation Pluridisciplinaire Marfan (C.M.; C. Boileau) and Laboratoire de Génétique Moléculaire (C. Boileau), Hôpital Ambroise Paré, Assistance Publique des Hôpitaux de Paris (APHP), Université Versailles–Saint Quentin en Yvelines, Boulogne, France; Service de Génétique, Hôtel Dieu, Lyon (H.P.); Institut für Medizinische Genetik, Universitätsmedizin Charité, Berlin (P.N.R.); Marfan Research Group (L.C.A.; A.B.; B.B.; M.B.; K.J.H.) and Departments of Clinical Genetics (L.C.A.) and Molecular Genetics (A.B.; B.B.; M.B.; K.J.H.) and Discipline of Paediatrics and Child Health (L.C.A.), The Children’s Hospital at Westmead, Sydney, Australia; Departments of Genetics and Pediatrics, Stanford University Medical Center, Stanford (U.F.); and Consultation Pluridisciplinaire Marfan, Hôpital Bichat, APHP, Paris (G.J.)</aff><author-notes><corresp>Address for correspondence and reprints: Pr. L. Faivre, Centre de Génétique, Hôpital d’Enfants, 10, boulevard Maréchal DeLattre de Tassigny, 21034 Dijon, France. E-mail: <email>laurence.faivre@chu-dijon.fr</email></corresp></author-notes><pub-date pub-type="ppub"><month>9</month><year>2007</year></pub-date><pub-date pub-type="epub"><day>25</day><month>7</month><year>2007</year></pub-date><volume>81</volume><issue>3</issue><fpage>454</fpage><lpage>466</lpage><history><date date-type="received"><day>17</day><month>1</month><year>2007</year></date><date date-type="accepted"><day>16</day><month>5</month><year>2007</year></date></history><copyright-statement>© 2007 by The American Society of Human Genetics. All rights reserved.</copyright-statement><copyright-year>2007</copyright-year><self-uri>17701892</self-uri><abstract><p>Mutations in the fibrillin-1 (<italic>FBN1</italic>) gene cause Marfan syndrome (MFS) and have been associated with a wide range of overlapping phenotypes. Clinical care is complicated by variable age at onset and the wide range of severity of aortic features. The factors that modulate phenotypical severity, both among and within families, remain to be determined. The availability of international <italic>FBN1</italic> mutation Universal Mutation Database (UMD-<italic>FBN1</italic>) has allowed us to perform the largest collaborative study ever reported, to investigate the correlation between the <italic>FBN1</italic> genotype and the nature and severity of the clinical phenotype. A range of qualitative and quantitative clinical parameters (skeletal, cardiovascular, ophthalmologic, skin, pulmonary, and dural) was compared for different classes of mutation (types and locations) in 1,013 probands with a pathogenic <italic>FBN1</italic> mutation. A higher probability of ectopia lentis was found for patients with a missense mutation substituting or producing a cysteine, when compared with other missense mutations. Patients with an <italic>FBN1</italic> premature termination codon had a more severe skeletal and skin phenotype than did patients with an inframe mutation. Mutations in exons 24–32 were associated with a more severe and complete phenotype, including younger age at diagnosis of type I fibrillinopathy and higher probability of developing ectopia lentis, ascending aortic dilatation, aortic surgery, mitral valve abnormalities, scoliosis, and shorter survival; the majority of these results were replicated even when cases of neonatal MFS were excluded. These correlations, found between different mutation types and clinical manifestations, might be explained by different underlying genetic mechanisms (dominant negative versus haploinsufficiency) and by consideration of the two main physiological functions of fibrillin-1 (structural versus mediator of TGFβ signalling). Exon 24–32 mutations define a high-risk group for cardiac manifestations associated with severe prognosis at all ages.</p></abstract></article-meta></front><floats-wrap><fig id="FG1" fig-type="EPS" position="float"><label>Figure 1. </label><caption><p>Types of <italic>FBN1</italic> mutations included in the study. Of 1,013, 573 (56%) could be classified as missense mutations, 170 (17%) as frameshift mutations, 137 (14%) as nonsense mutations, 110 (11%) as splicing mutations, and 23 (2%) as inframe deletions or insertions.</p></caption><graphic xlink:href="AJHGv81p454fg1"></graphic></fig><fig id="FG2" fig-type="EPS" position="float"><label>Figure 2. </label><caption><p>Kaplan-Meier analyses for the probability of ectopia lentis diagnoses for patients with different types of mutations. <italic>A,</italic> Probability of ectopia lentis in PTC versus inframe mutations. The cumulative probability of diagnosis of ectopia lentis before or at age 25 years was 23% (99.9% CI 15%–32%) for patients with PTC mutations (<italic>thin line</italic>) compared with 50% (99.9% CI 43%–57%) for patients with inframe mutations (<italic>thick line</italic>) (log-rank test <inline-formula><italic>P</italic><.0001</inline-formula>). <italic>B,</italic> Probability of ectopia lentis for patients with missense mutation involving a cysteine versus other missense mutations. The cumulative probability of diagnosis of ectopia lentis before or at age 25 years was 59% (99.9% CI 50%–68%) for patients with missense mutations involving a cysteine (<italic>thin line</italic>) compared with 32% (99.9% CI 22%–44%) for patients with other missense mutations (<italic>thick line</italic>) (log-rank test <inline-formula><italic>P</italic><.0001</inline-formula>).</p></caption><graphic xlink:href="AJHGv81p454fg2"></graphic></fig><fig id="FG3" fig-type="EPS" position="float"><label>Figure 3. </label><caption><p>Frequency of skeletal, skin, pulmonary, and dural phenotypes in study participants with PTC mutations (<italic>gray bars</italic>), compared with those with inframe mutations (<italic>black bars</italic>). An asterisk (*) indicates that differences between groups were statistically significant (MH test <inline-formula><italic>P</italic><.001</inline-formula>).</p></caption><graphic xlink:href="AJHGv81p454fg3"></graphic></fig><fig id="FG4" fig-type="EPS" position="float"><label>Figure 4. </label><caption><p>Kaplan-Meier analyses for the probability of MFS clinical-features diagnosis for patients with different locations of mutations. <italic>A,</italic> Age at diagnosis of type I fibrillinopathy with a mutation in exons 24–32 versus in other exons. Fifty percent of patients with a mutation in exons 24–32 (<italic>thin line</italic>) received a diagnosis at age 9 years (IQR 1–24 years) versus age 24 years (IQR 12–35 years) of patients with a mutation in other exons (<italic>thick line</italic>) (log-rank test <inline-formula><italic>P</italic><.0001</inline-formula>). <italic>B,</italic> Survival of patients with mutations in exons 24–32 versus in other exons. Seventy-six percent of patients with mutations within exons 24–32 (<italic>thin line</italic>) were alive at age 40 years (99.9%CI 61%–87% years) compared with 98% (99.9% CI 93%–99%) of patients with mutations located in other exons (<italic>thick line</italic>) (log-rank test <inline-formula><italic>P</italic><.0001</inline-formula>). <italic>C,</italic> Probability of diagnosing a dilatation of the ascending aorta for patients with mutations in exons 24–32 versus in other exons. The cumulative probability of diagnosis of ascending aortic dilatation before or at age 40 years was 87% (99.9% CI 77%–95%) for patients with mutations in exons 24–32 (<italic>thin line</italic>) compared with 72% (99.9% CI 67%–78%) for patients with mutations in other exons (<italic>thick line</italic>) (log-rank test <inline-formula><italic>P</italic><.0001</inline-formula>). <italic>D,</italic> Probability of aortic surgery for patients with mutations in exons 24–32 versus in other exons. The cumulative probability of aortic surgery before or at age 40 years was 55% (99.9% CI 35%–77%) for patients with mutations in exons 24–32 (<italic>thin line</italic>) compared with 38% (99.9% CI 30%–48%) for patients with mutations in other exons (<italic>thick line</italic>) (log-rank test <inline-formula><italic>P</italic><.0001</inline-formula>). <italic>E,</italic> Probability of ectopia lentis for patients with mutations in exons 24–32 versus in other exons. The cumulative probability of ectopia lentis diagnosis before or at age 25 years was 53% (99.9% CI 39%–67%) for patients with mutations in exons 24–32 (<italic>thin line</italic>) compared with 38% (99.9% CI 33%–44%) for patients with mutations in other exons (<italic>thick line</italic>) (log-rank test <inline-formula><italic>P</italic>=.0003</inline-formula>). <italic>F,</italic> Probability of scoliosis for patients with mutations in exons 24–32 versus in other exons. The cumulative probability of scoliosis diagnosis before or at age 25 years was 61% (99.9% CI 47%–75%) for patients with mutations in exons 24–32 (<italic>thin line</italic>) compared with 44% (99.9% CI 38%–51%) for patients with mutations in other exons (<italic>thick line</italic>) (log-rank test <inline-formula><italic>P</italic><.0001</inline-formula>).</p></caption><graphic xlink:href="AJHGv81p454fg4"></graphic></fig><table-wrap id="TB1"><label>Table 1. </label><caption><p>Number of Patients Recruited to the Study and Their Laboratory of Origin</p></caption><table frame="hsides" rules="groups"><col span="2"></col><thead><tr><td align="left" valign="bottom">Origin</td><td align="center" valign="bottom">No. of Patients (Laboratories)</td></tr></thead><tbody><tr><td align="left" valign="top">Belgium</td><td align="char" valign="top" char=".">167 (1)</td></tr><tr><td align="left" valign="top">United Kingdom</td><td align="char" valign="top" char=".">166 (7)</td></tr><tr><td align="left" valign="top">Germany</td><td align="char" valign="top" char=".">156 (4)</td></tr><tr><td align="left" valign="top">France</td><td align="char" valign="top" char=".">154 (3)</td></tr><tr><td align="left" valign="top">United States</td><td align="char" valign="top" char=".">146 (8)</td></tr><tr><td align="left" valign="top">Italy</td><td align="char" valign="top" char=".">89 (2)</td></tr><tr><td align="left" valign="top">Australia</td><td align="char" valign="top" char=".">80 (1)</td></tr><tr><td align="left" valign="top">Asia</td><td align="char" valign="top" char=".">22 (6)</td></tr><tr><td align="left" valign="top">Other European countries</td><td align="char" valign="top" char=".">22 (3)</td></tr><tr><td align="left" valign="top">Other North and South American countries</td><td align="char" valign="top" char=".">11 (2)</td></tr><tr><td align="left" valign="top"> Total</td><td align="char" valign="top" char=".">1,013 (37)</td></tr></tbody></table></table-wrap><table-wrap id="TB2"><label>Table 2. </label><caption><p>Frequency of Clinical Features in the Different Systems Involved in MFS and Type I Fibrillinopathies (<inline-formula><italic>N</italic>=1,013</inline-formula>)</p></caption><table frame="hsides" rules="groups"><col span="4"></col><thead><tr><td align="left" valign="bottom">System and Clinical Feature(s)</td><td align="center" valign="bottom">No. of Events</td><td align="center" valign="bottom">No. of<break></break>Available Data</td><td align="center" valign="bottom">Percentage</td></tr></thead><tbody><tr><td align="left" valign="bottom">Skeletal:</td><td align="char" valign="bottom" char="."></td><td align="char" valign="bottom" char="."></td><td align="char" valign="bottom" char="."></td></tr><tr><td align="left" valign="bottom"> Arachnodactyly</td><td align="char" valign="bottom" char=".">751</td><td align="char" valign="bottom" char=".">969<xref rid="TB2FNA" ref-type="table-fn">a</xref></td><td align="char" valign="bottom" char=".">78</td></tr><tr><td align="left" valign="bottom"> Dolichostenomelia</td><td align="char" valign="bottom" char=".">522</td><td align="char" valign="bottom" char=".">947<xref rid="TB2FNA" ref-type="table-fn">a</xref></td><td align="char" valign="bottom" char=".">55</td></tr><tr><td align="left" valign="bottom"> Joint laxity</td><td align="char" valign="bottom" char=".">600</td><td align="char" valign="bottom" char=".">956<xref rid="TB2FNA" ref-type="table-fn">a</xref></td><td align="char" valign="bottom" char=".">63</td></tr><tr><td align="left" valign="bottom"> Scoliosis</td><td align="char" valign="bottom" char=".">508</td><td align="char" valign="bottom" char=".">965<xref rid="TB2FNA" ref-type="table-fn">a</xref></td><td align="char" valign="bottom" char=".">53</td></tr><tr><td align="left" valign="bottom"> Pectus deformity<xref rid="TB2FNB" ref-type="table-fn">b</xref></td><td align="char" valign="bottom" char=".">570</td><td align="char" valign="bottom" char=".">962<xref rid="TB2FNA" ref-type="table-fn">a</xref></td><td align="char" valign="bottom" char=".">59</td></tr><tr><td align="left" valign="bottom"> Limited elbow extension</td><td align="char" valign="bottom" char=".">153</td><td align="char" valign="bottom" char=".">974<xref rid="TB2FNA" ref-type="table-fn">a</xref></td><td align="char" valign="bottom" char=".">16</td></tr><tr><td align="left" valign="bottom"> Protrusio acetabulae</td><td align="char" valign="bottom" char=".">69</td><td align="char" valign="bottom" char=".">298<xref rid="TB2FNA" ref-type="table-fn">a</xref></td><td align="char" valign="bottom" char=".">23</td></tr><tr><td align="left" valign="bottom"> Facial dysmorphism</td><td align="char" valign="bottom" char=".">443</td><td align="char" valign="bottom" char=".">913<xref rid="TB2FNA" ref-type="table-fn">a</xref></td><td align="char" valign="bottom" char=".">49</td></tr><tr><td align="left" valign="bottom"> High-arched palate</td><td align="char" valign="bottom" char=".">639</td><td align="char" valign="bottom" char=".">932<xref rid="TB2FNA" ref-type="table-fn">a</xref></td><td align="char" valign="bottom" char=".">69</td></tr><tr><td align="left" valign="bottom"> Dental malocclusion</td><td align="char" valign="bottom" char=".">372</td><td align="char" valign="bottom" char=".">843<xref rid="TB2FNA" ref-type="table-fn">a</xref></td><td align="char" valign="bottom" char=".">44</td></tr><tr><td align="left" valign="bottom"> Pes planus</td><td align="char" valign="bottom" char=".">402</td><td align="char" valign="bottom" char=".">864<xref rid="TB2FNA" ref-type="table-fn">a</xref></td><td align="char" valign="bottom" char=".">47</td></tr><tr><td align="left" valign="bottom"> Orthopedic surgery</td><td align="char" valign="bottom" char=".">113</td><td align="char" valign="bottom" char=".">983<xref rid="TB2FNA" ref-type="table-fn">a</xref></td><td align="char" valign="bottom" char=".">12</td></tr><tr><td align="left" valign="bottom"> Major skeletal involvement</td><td align="char" valign="bottom" char=".">327</td><td align="char" valign="bottom" char=".">1,013</td><td align="char" valign="bottom" char=".">32</td></tr><tr><td align="left" valign="bottom"> Minor skeletal involvement</td><td align="char" valign="bottom" char=".">564</td><td align="char" valign="bottom" char=".">1,013</td><td align="char" valign="bottom" char=".">56</td></tr><tr><td align="left" valign="bottom">Ocular:</td><td align="char" valign="bottom" char="."></td><td align="char" valign="bottom" char="."></td><td align="char" valign="bottom" char="."></td></tr><tr><td align="left" valign="bottom"> Ectopia lentis</td><td align="char" valign="bottom" char=".">542</td><td align="char" valign="bottom" char=".">1,013</td><td align="char" valign="bottom" char=".">54</td></tr><tr><td align="left" valign="bottom"> Myopia</td><td align="char" valign="bottom" char=".">453</td><td align="char" valign="bottom" char=".">865</td><td align="char" valign="bottom" char=".">52</td></tr><tr><td align="left" valign="bottom"> Cataract</td><td align="char" valign="bottom" char=".">39</td><td align="char" valign="bottom" char=".">983</td><td align="char" valign="bottom" char=".">4</td></tr><tr><td align="left" valign="bottom"> Retinal detachment</td><td align="char" valign="bottom" char=".">65</td><td align="char" valign="bottom" char=".">980</td><td align="char" valign="bottom" char=".">7</td></tr><tr><td align="left" valign="bottom"> Glaucoma</td><td align="char" valign="bottom" char=".">19</td><td align="char" valign="bottom" char=".">905</td><td align="char" valign="bottom" char=".">2</td></tr><tr><td align="left" valign="bottom"> Surgery for ectopia lentis</td><td align="char" valign="bottom" char=".">122</td><td align="char" valign="bottom" char=".">910</td><td align="char" valign="bottom" char=".">13</td></tr><tr><td align="left" valign="bottom"> Other eye surgeries</td><td align="char" valign="bottom" char=".">43</td><td align="char" valign="bottom" char=".">905</td><td align="char" valign="bottom" char=".">5</td></tr><tr><td align="left" valign="bottom"> Major eye involvement</td><td align="char" valign="bottom" char=".">542</td><td align="char" valign="bottom" char=".">1,013</td><td align="char" valign="bottom" char=".">54</td></tr><tr><td align="left" valign="bottom">Cardiac:</td><td align="char" valign="bottom" char="."></td><td align="char" valign="bottom" char="."></td><td align="char" valign="bottom" char="."></td></tr><tr><td align="left" valign="bottom"> Dilatation of the ascending aorta</td><td align="char" valign="bottom" char=".">775</td><td align="char" valign="bottom" char=".">1,013</td><td align="char" valign="bottom" char=".">77</td></tr><tr><td align="left" valign="bottom"> Dissection of the ascending aorta</td><td align="char" valign="bottom" char=".">145</td><td align="char" valign="bottom" char=".">1,013</td><td align="char" valign="bottom" char=".">14</td></tr><tr><td align="left" valign="bottom"> Dilatation or dissection of the descending or abdominal aorta before age 50 years</td><td align="char" valign="bottom" char=".">66</td><td align="char" valign="bottom" char=".">1,013</td><td align="char" valign="bottom" char=".">7</td></tr><tr><td align="left" valign="bottom"> Mitral valve prolapse</td><td align="char" valign="bottom" char=".">533</td><td align="char" valign="bottom" char=".">983</td><td align="char" valign="bottom" char=".">54</td></tr><tr><td align="left" valign="bottom"> Mitral regurgitation</td><td align="char" valign="bottom" char=".">313</td><td align="char" valign="bottom" char=".">959</td><td align="char" valign="bottom" char=".">33</td></tr><tr><td align="left" valign="bottom"> Aortic insufficiency</td><td align="char" valign="bottom" char=".">205</td><td align="char" valign="bottom" char=".">975</td><td align="char" valign="bottom" char=".">21</td></tr><tr><td align="left" valign="bottom"> Aortic surgery</td><td align="char" valign="bottom" char=".">282</td><td align="char" valign="bottom" char=".">1011</td><td align="char" valign="bottom" char=".">28</td></tr><tr><td align="left" valign="bottom"> Isolated valvular surgery</td><td align="char" valign="bottom" char=".">45</td><td align="char" valign="bottom" char=".">1004</td><td align="char" valign="bottom" char=".">4</td></tr><tr><td align="left" valign="bottom"> Major cardiac involvement</td><td align="char" valign="bottom" char=".">776</td><td align="char" valign="bottom" char=".">1,013</td><td align="char" valign="bottom" char=".">77</td></tr><tr><td align="left" valign="bottom"> Minor cardiac involvement</td><td align="char" valign="bottom" char=".">108</td><td align="char" valign="bottom" char=".">1,013</td><td align="char" valign="bottom" char=".">11</td></tr><tr><td align="left" valign="bottom">Skin:</td><td align="char" valign="bottom" char="."></td><td align="char" valign="bottom" char="."></td><td align="char" valign="bottom" char="."></td></tr><tr><td align="left" valign="bottom"> Striae</td><td align="char" valign="bottom" char=".">444</td><td align="char" valign="bottom" char=".">945</td><td align="char" valign="bottom" char=".">47</td></tr><tr><td align="left" valign="bottom"> Herniae</td><td align="char" valign="bottom" char=".">96</td><td align="char" valign="bottom" char=".">988</td><td align="char" valign="bottom" char=".">10</td></tr><tr><td align="left" valign="bottom"> Minor skin involvement</td><td align="char" valign="bottom" char=".">480</td><td align="char" valign="bottom" char=".">1,013</td><td align="char" valign="bottom" char=".">47</td></tr><tr><td align="left" valign="bottom">Lung:</td><td align="char" valign="bottom" char="."></td><td align="char" valign="bottom" char="."></td><td align="char" valign="bottom" char="."></td></tr><tr><td align="left" valign="bottom"> Pneumothorax</td><td align="char" valign="bottom" char=".">73</td><td align="char" valign="bottom" char=".">1,002</td><td align="char" valign="bottom" char=".">7</td></tr><tr><td align="left" valign="bottom"> Minor lung involvement</td><td align="char" valign="bottom" char=".">73</td><td align="char" valign="bottom" char=".">1,013</td><td align="char" valign="bottom" char=".">7</td></tr><tr><td align="left" valign="bottom">CNS:</td><td align="char" valign="bottom" char="."></td><td align="char" valign="bottom" char="."></td><td align="char" valign="bottom" char="."></td></tr><tr><td align="left" valign="bottom"> Dural ectasia</td><td align="char" valign="bottom" char=".">154</td><td align="char" valign="bottom" char=".">292</td><td align="char" valign="bottom" char=".">53</td></tr><tr><td align="left" valign="bottom"> Major CNS involvement</td><td align="char" valign="bottom" char=".">154</td><td align="char" valign="bottom" char=".">1,013</td><td align="char" valign="bottom" char=".">15</td></tr></tbody></table><table-wrap-foot><fn id="TB2FNA"><label>a</label><p>Nineteen patients were classified as having minor, major, or neither minor nor major skeletal features, but details about their skeletal manifestations were not available.</p></fn><fn id="TB2FNB"><label>b</label><p>Includes pectus excavatum, 246 (26%) of 962; pectus carinatum, 288 (30%) of 962; and undefined pectus malformation.</p></fn></table-wrap-foot></table-wrap><table-wrap id="TB3"><label>Table 3. </label><caption><p>Comparison of Probabilities of Clinical-Feature Diagnosis at a Specific Age for Patients with MFS and Other Type I Fibrillinopathies, According to the Type or Location of <italic>FBN1</italic> Mutations<xref ref-type="table-fn" rid="N0xfd5afd0N0x2ae1c30">[Note]</xref></p></caption><table frame="hsides" rules="groups"><col span="12"></col><thead><tr><td align="center" valign="bottom"></td><td align="center" valign="bottom"></td><td align="center" valign="bottom">Frequency</td><td colspan="3" align="center" valign="bottom">Probabilities ofClinical FeaturesDiagnosis (%) at Age<hr></hr></td><td align="center" valign="bottom"></td><td align="center" valign="bottom">Frequency</td><td colspan="3" align="center" valign="bottom">Probabilities ofClinical FeaturesDiagnosis (%) at Age<hr></hr></td><td align="center" valign="bottom"></td></tr><tr><td align="center" valign="bottom"></td><td align="center" valign="bottom"><italic>n</italic><hr></hr></td><td align="center" valign="bottom">(%)<hr></hr></td><td align="center" valign="bottom">10<hr></hr></td><td align="center" valign="bottom">25<hr></hr></td><td align="center" valign="bottom">40<hr></hr></td><td align="center" valign="bottom"><italic>n</italic><hr></hr></td><td align="center" valign="bottom">(%)<hr></hr></td><td align="center" valign="bottom">10<hr></hr></td><td align="center" valign="bottom">25<hr></hr></td><td align="center" valign="bottom">40<hr></hr></td><td align="center" valign="bottom"></td></tr><tr><td align="center" valign="bottom">Clinical Feature</td><td colspan="5" align="center" valign="bottom">PTC Mutations</td><td colspan="5" align="center" valign="bottom">Inframe Mutations</td><td align="center" valign="bottom"><italic>P</italic><xref rid="TB3FNA" ref-type="table-fn">a</xref></td></tr></thead><tbody><tr><td align="left" valign="top">Age at diagnosis of type I fibrillinopathy</td><td align="char" valign="top" char=".">319</td><td align="char" valign="top" char=".">100.0</td><td align="char" valign="top" char=".">20.4</td><td align="char" valign="top" char=".">51.7</td><td align="char" valign="top" char=".">85.2</td><td align="char" valign="top" char=".">665</td><td align="char" valign="top" char=".">100.0</td><td align="char" valign="top" char=".">32.3</td><td align="char" valign="top" char=".">61.2</td><td align="char" valign="top" char=".">86.9</td><td align="char" valign="top" char=".">.0103</td></tr><tr><td align="left" valign="top">Ascending aortic dilatation</td><td align="char" valign="top" char=".">259</td><td align="char" valign="top" char=".">81.2</td><td align="char" valign="top" char=".">10.6</td><td align="char" valign="top" char=".">38.7</td><td align="char" valign="top" char=".">76.9</td><td align="char" valign="top" char=".">491</td><td align="char" valign="top" char=".">73.8</td><td align="char" valign="top" char=".">20.2</td><td align="char" valign="top" char=".">43.5</td><td align="char" valign="top" char=".">73.8</td><td align="char" valign="top" char=".">.7791</td></tr><tr><td align="left" valign="top">Aortic dissection in the population presenting with ascending aortic dilatation</td><td align="char" valign="top" char=".">65</td><td align="char" valign="top" char=".">25.1</td><td align="char" valign="top" char=".">.0</td><td align="char" valign="top" char=".">3.6</td><td align="char" valign="top" char=".">31.1</td><td align="char" valign="top" char=".">78</td><td align="char" valign="top" char=".">15.9</td><td align="char" valign="top" char=".">.2</td><td align="char" valign="top" char=".">5.1</td><td align="char" valign="top" char=".">22.9</td><td align="char" valign="top" char=".">.2014</td></tr><tr><td align="left" valign="top">Aortic surgery in the population presenting with ascending aortic dilatation</td><td align="char" valign="top" char=".">102</td><td align="char" valign="top" char=".">39.4</td><td align="char" valign="top" char=".">.0</td><td align="char" valign="top" char=".">9.4</td><td align="char" valign="top" char=".">42.0</td><td align="char" valign="top" char=".">147</td><td align="char" valign="top" char=".">29.9</td><td align="char" valign="top" char=".">1.8</td><td align="char" valign="top" char=".">12.2</td><td align="char" valign="top" char=".">40.4</td><td align="char" valign="top" char=".">.5301</td></tr><tr><td align="left" valign="top">Survival</td><td align="char" valign="top" char=".">303<hr></hr></td><td align="char" valign="top" char=".">95.0<hr></hr></td><td align="char" valign="top" char=".">99.7<hr></hr></td><td align="char" valign="top" char=".">98.8<hr></hr></td><td align="char" valign="top" char=".">95.1<hr></hr></td><td align="char" valign="top" char=".">43<hr></hr></td><td align="char" valign="top" char=".">6.5<hr></hr></td><td align="char" valign="top" char=".">95.5<hr></hr></td><td align="char" valign="top" char=".">94.4<hr></hr></td><td align="char" valign="top" char=".">93.2<hr></hr></td><td align="char" valign="top" char=".">.2311<hr></hr></td></tr><tr><td align="char" valign="bottom" char="."></td><td colspan="5" align="center" valign="bottom">Missense Mutations Involving a Cysteine<hr></hr></td><td colspan="5" align="center" valign="bottom">Other Missense Mutations<hr></hr></td><td align="center" valign="bottom"></td></tr><tr><td align="left" valign="top">Age at diagnosis of type I fibrillinopathy</td><td align="char" valign="top" char=".">348</td><td align="char" valign="top" char=".">100.0</td><td align="char" valign="top" char=".">32.8</td><td align="char" valign="top" char=".">62.6</td><td align="char" valign="top" char=".">89.1</td><td align="char" valign="top" char=".">225</td><td align="char" valign="top" char=".">100.0</td><td align="char" valign="top" char=".">28.9</td><td align="char" valign="top" char=".">57.8</td><td align="char" valign="top" char=".">82.2</td><td align="char" valign="top" char=".">.0983</td></tr><tr><td align="left" valign="top">Ascending aortic dilatation</td><td align="char" valign="top" char=".">262</td><td align="char" valign="top" char=".">75.3</td><td align="char" valign="top" char=".">21.3</td><td align="char" valign="top" char=".">46.3</td><td align="char" valign="top" char=".">75.6</td><td align="char" valign="top" char=".">158</td><td align="char" valign="top" char=".">70.2</td><td align="char" valign="top" char=".">17.6</td><td align="char" valign="top" char=".">37.4</td><td align="char" valign="top" char=".">69.4</td><td align="char" valign="top" char=".">.0797</td></tr><tr><td align="left" valign="top">Aortic dissection in the population presenting with ascending aortic dilatation</td><td align="char" valign="top" char=".">41</td><td align="char" valign="top" char=".">15.6</td><td align="char" valign="top" char=".">.0</td><td align="char" valign="top" char=".">4.6</td><td align="char" valign="top" char=".">29.9</td><td align="char" valign="top" char=".">25</td><td align="char" valign="top" char=".">15.8</td><td align="char" valign="top" char=".">.7</td><td align="char" valign="top" char=".">5.2</td><td align="char" valign="top" char=".">10.8</td><td align="char" valign="top" char=".">.4249</td></tr><tr><td align="left" valign="top">Aortic surgery in the population presenting with ascending aortic dilatation</td><td align="char" valign="top" char=".">80</td><td align="char" valign="top" char=".">30.5</td><td align="char" valign="top" char=".">1.3</td><td align="char" valign="top" char=".">14.0</td><td align="char" valign="top" char=".">47.4</td><td align="char" valign="top" char=".">49</td><td align="char" valign="top" char=".">31.0</td><td align="char" valign="top" char=".">2.7</td><td align="char" valign="top" char=".">10.4</td><td align="char" valign="top" char=".">29.0</td><td align="char" valign="top" char=".">.2712</td></tr><tr><td align="left" valign="top">Survival</td><td align="char" valign="top" char=".">330<hr></hr></td><td align="char" valign="top" char=".">94.8<hr></hr></td><td align="char" valign="top" char=".">96.5<hr></hr></td><td align="char" valign="top" char=".">96.1<hr></hr></td><td align="char" valign="top" char=".">94.5<hr></hr></td><td align="char" valign="top" char=".">14<hr></hr></td><td align="char" valign="top" char=".">6.2<hr></hr></td><td align="char" valign="top" char=".">96.0<hr></hr></td><td align="char" valign="top" char=".">93.5<hr></hr></td><td align="char" valign="top" char=".">93.5<hr></hr></td><td align="char" valign="top" char=".">.6785<hr></hr></td></tr><tr><td align="char" valign="bottom" char="."></td><td colspan="5" align="center" valign="bottom">Exons 24–32<hr></hr></td><td colspan="5" align="center" valign="bottom">Other Exons<hr></hr></td><td align="char" valign="bottom" char="."></td></tr><tr><td align="left" valign="top">Age at diagnosis of type I fibrillinopathy</td><td align="char" valign="top" char=".">198</td><td align="char" valign="top" char=".">100.0</td><td align="char" valign="top" char=".">51.0</td><td align="char" valign="top" char=".">75.8</td><td align="char" valign="top" char=".">91.9</td><td align="char" valign="top" char=".">815</td><td align="char" valign="top" char=".">100.0</td><td align="char" valign="top" char=".">23.1</td><td align="char" valign="top" char=".">53.7</td><td align="char" valign="top" char=".">85.2</td><td align="char" valign="top" char="."><.0001</td></tr><tr><td align="left" valign="top">Ascending aortic dilatation</td><td align="char" valign="top" char=".">164</td><td align="char" valign="top" char=".">82.8</td><td align="char" valign="top" char=".">42.5</td><td align="char" valign="top" char=".">65.7</td><td align="char" valign="top" char=".">87.3</td><td align="char" valign="top" char=".">609</td><td align="char" valign="top" char=".">74.7</td><td align="char" valign="top" char=".">11.3</td><td align="char" valign="top" char=".">36.4</td><td align="char" valign="top" char=".">72.4</td><td align="char" valign="top" char="."><.0001</td></tr><tr><td align="left" valign="top">Aortic dissection in the population presenting with ascending aortic dilatation</td><td align="char" valign="top" char=".">21</td><td align="char" valign="top" char=".">12.8</td><td align="char" valign="top" char=".">.7</td><td align="char" valign="top" char=".">5.8</td><td align="char" valign="top" char=".">28.5</td><td align="char" valign="top" char=".">124</td><td align="char" valign="top" char=".">20.4</td><td align="char" valign="top" char=".">.2</td><td align="char" valign="top" char=".">4.3</td><td align="char" valign="top" char=".">25.7</td><td align="char" valign="top" char=".">.3064</td></tr><tr><td align="left" valign="top">Aortic surgery in the population presenting with ascending aortic dilatation</td><td align="char" valign="top" char=".">52</td><td align="char" valign="top" char=".">31.7</td><td align="char" valign="top" char=".">4.7</td><td align="char" valign="top" char=".">17.5</td><td align="char" valign="top" char=".">55.2</td><td align="char" valign="top" char=".">201</td><td align="char" valign="top" char=".">33.0</td><td align="char" valign="top" char=".">.5</td><td align="char" valign="top" char=".">9.9</td><td align="char" valign="top" char=".">38.4</td><td align="char" valign="top" char="."><.0001</td></tr><tr><td align="left" valign="top">Survival</td><td align="char" valign="top" char=".">159</td><td align="char" valign="top" char=".">80.3</td><td align="char" valign="top" char=".">84.5</td><td align="char" valign="top" char=".">81.1</td><td align="char" valign="top" char=".">76.1</td><td align="char" valign="top" char=".">22</td><td align="char" valign="top" char=".">2.7</td><td align="char" valign="top" char=".">99.6</td><td align="char" valign="top" char=".">99.1</td><td align="char" valign="top" char=".">97.5</td><td align="char" valign="top" char="."><.0001</td></tr></tbody></table><table-wrap-foot><fn id="N0xfd5afd0N0x2ae1c30"><p><sc>Note.—</sc> All ages are in years. Results are Kaplan-Meier estimates.</p></fn><fn id="TB3FNA"><label>a</label><p>Log-rank test <italic>P</italic> values were for PTC mutations versus inframe mutations, for missense mutations involving a cysteine versus other missense mutations, or for mutations within exons 24–32 versus mutations in other exons.</p></fn></table-wrap-foot></table-wrap><table-wrap id="TB4"><label>Table 4. </label><caption><p>Types of Mutations Found in Exons 24–32, Compared with Mutations in the Other Exons<xref ref-type="table-fn" rid="N0xfd5afd0N0x2ae2218">[Note]</xref></p></caption><table frame="hsides" rules="groups"><col span="3"></col><thead><tr><td align="left" valign="bottom"></td><td colspan="2" align="center" valign="bottom">No. (%) of Mutations in<hr></hr></td></tr><tr><td align="left" valign="bottom">Mutation</td><td align="center" valign="bottom">Exons 24–32<break></break>(<inline-formula><italic>n</italic>=198</inline-formula>)</td><td align="center" valign="bottom">Other Exons<break></break>(<inline-formula><italic>n</italic>=815</inline-formula>)</td></tr></thead><tbody><tr><td align="left" valign="top">Nonsense</td><td align="char" valign="top" char=".">13 (6.6)</td><td align="char" valign="top" char=".">124 (15.2)</td></tr><tr><td align="left" valign="top">Frameshift</td><td align="char" valign="top" char=".">27 (13.6)</td><td align="char" valign="top" char=".">143 (17.5)</td></tr><tr><td align="left" valign="top">Splicing</td><td align="char" valign="top" char=".">15 (7.6)</td><td align="char" valign="top" char=".">95 (11.7)</td></tr><tr><td align="left" valign="top">Missense</td><td align="char" valign="top" char=".">139 (70.2<xref rid="TB4FNA" ref-type="table-fn">a</xref>)</td><td align="char" valign="top" char=".">434 (53.3<xref rid="TB4FNB" ref-type="table-fn">b</xref>)</td></tr><tr><td align="left" valign="top">Inframe deletion/insertion</td><td align="char" valign="top" char=".">4 (2.0)</td><td align="char" valign="top" char=".">19 (2.3)</td></tr></tbody></table><table-wrap-foot><fn id="N0xfd5afd0N0x2ae2218"><p><sc>Note.—</sc> Global Fischer exact test for differences was used, according to the location of mutations. <inline-formula><italic>P</italic>=.0002</inline-formula>.</p></fn><fn id="TB4FNA"><label>a</label><p>54% involving a cysteine.</p></fn><fn id="TB4FNB"><label>b</label><p>63% involving a cysteine.</p></fn></table-wrap-foot></table-wrap></floats-wrap></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Asie/explor/AustralieFrV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 0000381 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 0000381 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Asie
|area= AustralieFrV1
|flux= Pmc
|étape= Corpus
|type= RBID
|clé=
|texte=
}}
| This area was generated with Dilib version V0.6.33. |  |