A homozygous B3GAT3 mutation causes a severe syndrome with multiple fractures, expanding the phenotype of linkeropathy syndromes.
Identifieur interne : 000E31 ( PubMed/Corpus ); précédent : 000E30; suivant : 000E32A homozygous B3GAT3 mutation causes a severe syndrome with multiple fractures, expanding the phenotype of linkeropathy syndromes.
Auteurs : Kelly L. Jones ; Ulrike Schwarze ; Margaret P. Adam ; Peter H. Byers ; Heather C. MeffordSource :
- American journal of medical genetics. Part A [ 1552-4833 ] ; 2015.
English descriptors
- KwdEn :
- MESH :
- chemical , genetics : Glucuronosyltransferase.
- diagnostic imaging : Fractures, Multiple.
- genetics : Fractures, Multiple, Mutation.
- Genetic Testing, Homozygote, Humans, Infant, Infant, Newborn, Male, Phenotype, Radiography, Syndrome.
Abstract
Linkeropathies are a group of syndromes characterized by short stature, radio-ulnar synostosis, decreased bone density, congenital contractures and dislocations, joint laxity, broad digits, brachycephaly, small mouth, prominent eyes, short or webbed neck, congenital heart defects and mild developmental delay. Linkeropathies are due to enzymatic defects in the synthesis of the common linker region that joins the core proteins to their glycosaminoglycan (GAG) side chains. The enzyme glucuronyltransferase 1, encoded by B3GAT3, adds the last four saccharides comprising the linker region. Mutations in B3GAT3 have been reported in two unrelated families with the same homozygous mutation (c.830G>A, p.Arg277Gln). We report on a patient with a novel homozygous B3GAT3 (c.667G>A, p.Gly223Ser) mutation and a history of multiple fractures, blue sclerae, and glaucoma. Our patient was a 12-month-old boy born to consanguineous parents and, like previously reported patients, he had bilateral radio-ulnar synostosis, severe osteopenia, an increased gap between first and second toes, bilateral club feet, and atrial and ventricular septal defects. He had the additional features of bilateral glaucoma, hypertelorism, upturned nose with anteverted nares, a small chest, a diaphragmatic hernia, multiple fractures, arachnodactyly, overlapping fingers with ulnar deviation, lymphedema, hypotonia, hearing loss, and perinatal cerebral infarction with bilateral supra- and infratentorial subdural hematomas. We highlight the extended phenotypic range of B3GAT3 mutations and a provide comparative overview of the phenotypic features of the linkeropathies associated with mutations in XYLT1, B4GALT7, B3GALT6, and B3GAT3.
DOI: 10.1002/ajmg.a.37209
PubMed: 26086840
Links to Exploration step
pubmed:26086840Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A homozygous B3GAT3 mutation causes a severe syndrome with multiple fractures, expanding the phenotype of linkeropathy syndromes.</title><author><name sortKey="Jones, Kelly L" sort="Jones, Kelly L" uniqKey="Jones K" first="Kelly L" last="Jones">Kelly L. Jones</name><affiliation><nlm:affiliation>Division of Genetic Medicine, Department of Pediatrics, University of Washington & Seattle Children's Hospital, Seattle, Washington.</nlm:affiliation></affiliation></author><author><name sortKey="Schwarze, Ulrike" sort="Schwarze, Ulrike" uniqKey="Schwarze U" first="Ulrike" last="Schwarze">Ulrike Schwarze</name><affiliation><nlm:affiliation>Department of Pathology, University of Washington, Seattle, Washington.</nlm:affiliation></affiliation></author><author><name sortKey="Adam, Margaret P" sort="Adam, Margaret P" uniqKey="Adam M" first="Margaret P" last="Adam">Margaret P. Adam</name><affiliation><nlm:affiliation>Division of Genetic Medicine, Department of Pediatrics, University of Washington & Seattle Children's Hospital, Seattle, Washington.</nlm:affiliation></affiliation></author><author><name sortKey="Byers, Peter H" sort="Byers, Peter H" uniqKey="Byers P" first="Peter H" last="Byers">Peter H. Byers</name><affiliation><nlm:affiliation>Department of Pathology, University of Washington, Seattle, Washington.</nlm:affiliation></affiliation></author><author><name sortKey="Mefford, Heather C" sort="Mefford, Heather C" uniqKey="Mefford H" first="Heather C" last="Mefford">Heather C. Mefford</name><affiliation><nlm:affiliation>Division of Genetic Medicine, Department of Pediatrics, University of Washington & Seattle Children's Hospital, Seattle, Washington.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2015">2015</date><idno type="RBID">pubmed:26086840</idno><idno type="pmid">26086840</idno><idno type="doi">10.1002/ajmg.a.37209</idno><idno type="wicri:Area/PubMed/Corpus">000E31</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000E31</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">A homozygous B3GAT3 mutation causes a severe syndrome with multiple fractures, expanding the phenotype of linkeropathy syndromes.</title><author><name sortKey="Jones, Kelly L" sort="Jones, Kelly L" uniqKey="Jones K" first="Kelly L" last="Jones">Kelly L. Jones</name><affiliation><nlm:affiliation>Division of Genetic Medicine, Department of Pediatrics, University of Washington & Seattle Children's Hospital, Seattle, Washington.</nlm:affiliation></affiliation></author><author><name sortKey="Schwarze, Ulrike" sort="Schwarze, Ulrike" uniqKey="Schwarze U" first="Ulrike" last="Schwarze">Ulrike Schwarze</name><affiliation><nlm:affiliation>Department of Pathology, University of Washington, Seattle, Washington.</nlm:affiliation></affiliation></author><author><name sortKey="Adam, Margaret P" sort="Adam, Margaret P" uniqKey="Adam M" first="Margaret P" last="Adam">Margaret P. Adam</name><affiliation><nlm:affiliation>Division of Genetic Medicine, Department of Pediatrics, University of Washington & Seattle Children's Hospital, Seattle, Washington.</nlm:affiliation></affiliation></author><author><name sortKey="Byers, Peter H" sort="Byers, Peter H" uniqKey="Byers P" first="Peter H" last="Byers">Peter H. Byers</name><affiliation><nlm:affiliation>Department of Pathology, University of Washington, Seattle, Washington.</nlm:affiliation></affiliation></author><author><name sortKey="Mefford, Heather C" sort="Mefford, Heather C" uniqKey="Mefford H" first="Heather C" last="Mefford">Heather C. Mefford</name><affiliation><nlm:affiliation>Division of Genetic Medicine, Department of Pediatrics, University of Washington & Seattle Children's Hospital, Seattle, Washington.</nlm:affiliation></affiliation></author></analytic><series><title level="j">American journal of medical genetics. Part A</title><idno type="eISSN">1552-4833</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Fractures, Multiple (diagnostic imaging)</term><term>Fractures, Multiple (genetics)</term><term>Genetic Testing</term><term>Glucuronosyltransferase (genetics)</term><term>Homozygote</term><term>Humans</term><term>Infant</term><term>Infant, Newborn</term><term>Male</term><term>Mutation (genetics)</term><term>Phenotype</term><term>Radiography</term><term>Syndrome</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Glucuronosyltransferase</term></keywords><keywords scheme="MESH" qualifier="diagnostic imaging" xml:lang="en"><term>Fractures, Multiple</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Fractures, Multiple</term><term>Mutation</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Genetic Testing</term><term>Homozygote</term><term>Humans</term><term>Infant</term><term>Infant, Newborn</term><term>Male</term><term>Phenotype</term><term>Radiography</term><term>Syndrome</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Linkeropathies are a group of syndromes characterized by short stature, radio-ulnar synostosis, decreased bone density, congenital contractures and dislocations, joint laxity, broad digits, brachycephaly, small mouth, prominent eyes, short or webbed neck, congenital heart defects and mild developmental delay. Linkeropathies are due to enzymatic defects in the synthesis of the common linker region that joins the core proteins to their glycosaminoglycan (GAG) side chains. The enzyme glucuronyltransferase 1, encoded by B3GAT3, adds the last four saccharides comprising the linker region. Mutations in B3GAT3 have been reported in two unrelated families with the same homozygous mutation (c.830G>A, p.Arg277Gln). We report on a patient with a novel homozygous B3GAT3 (c.667G>A, p.Gly223Ser) mutation and a history of multiple fractures, blue sclerae, and glaucoma. Our patient was a 12-month-old boy born to consanguineous parents and, like previously reported patients, he had bilateral radio-ulnar synostosis, severe osteopenia, an increased gap between first and second toes, bilateral club feet, and atrial and ventricular septal defects. He had the additional features of bilateral glaucoma, hypertelorism, upturned nose with anteverted nares, a small chest, a diaphragmatic hernia, multiple fractures, arachnodactyly, overlapping fingers with ulnar deviation, lymphedema, hypotonia, hearing loss, and perinatal cerebral infarction with bilateral supra- and infratentorial subdural hematomas. We highlight the extended phenotypic range of B3GAT3 mutations and a provide comparative overview of the phenotypic features of the linkeropathies associated with mutations in XYLT1, B4GALT7, B3GALT6, and B3GAT3.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">26086840</PMID><DateCreated><Year>2015</Year><Month>10</Month><Day>20</Day></DateCreated><DateCompleted><Year>2016</Year><Month>08</Month><Day>29</Day></DateCompleted><DateRevised><Year>2016</Year><Month>11</Month><Day>25</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1552-4833</ISSN><JournalIssue CitedMedium="Internet"><Volume>167A</Volume><Issue>11</Issue><PubDate><Year>2015</Year><Month>Nov</Month></PubDate></JournalIssue><Title>American journal of medical genetics. Part A</Title><ISOAbbreviation>Am. J. Med. Genet. A</ISOAbbreviation></Journal><ArticleTitle>A homozygous B3GAT3 mutation causes a severe syndrome with multiple fractures, expanding the phenotype of linkeropathy syndromes.</ArticleTitle><Pagination><MedlinePgn>2691-6</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1002/ajmg.a.37209</ELocationID><Abstract><AbstractText>Linkeropathies are a group of syndromes characterized by short stature, radio-ulnar synostosis, decreased bone density, congenital contractures and dislocations, joint laxity, broad digits, brachycephaly, small mouth, prominent eyes, short or webbed neck, congenital heart defects and mild developmental delay. Linkeropathies are due to enzymatic defects in the synthesis of the common linker region that joins the core proteins to their glycosaminoglycan (GAG) side chains. The enzyme glucuronyltransferase 1, encoded by B3GAT3, adds the last four saccharides comprising the linker region. Mutations in B3GAT3 have been reported in two unrelated families with the same homozygous mutation (c.830G>A, p.Arg277Gln). We report on a patient with a novel homozygous B3GAT3 (c.667G>A, p.Gly223Ser) mutation and a history of multiple fractures, blue sclerae, and glaucoma. Our patient was a 12-month-old boy born to consanguineous parents and, like previously reported patients, he had bilateral radio-ulnar synostosis, severe osteopenia, an increased gap between first and second toes, bilateral club feet, and atrial and ventricular septal defects. He had the additional features of bilateral glaucoma, hypertelorism, upturned nose with anteverted nares, a small chest, a diaphragmatic hernia, multiple fractures, arachnodactyly, overlapping fingers with ulnar deviation, lymphedema, hypotonia, hearing loss, and perinatal cerebral infarction with bilateral supra- and infratentorial subdural hematomas. We highlight the extended phenotypic range of B3GAT3 mutations and a provide comparative overview of the phenotypic features of the linkeropathies associated with mutations in XYLT1, B4GALT7, B3GALT6, and B3GAT3.</AbstractText><CopyrightInformation>© 2015 Wiley Periodicals, Inc.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Jones</LastName><ForeName>Kelly L</ForeName><Initials>KL</Initials><AffiliationInfo><Affiliation>Division of Genetic Medicine, Department of Pediatrics, University of Washington & Seattle Children's Hospital, Seattle, Washington.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Schwarze</LastName><ForeName>Ulrike</ForeName><Initials>U</Initials><AffiliationInfo><Affiliation>Department of Pathology, University of Washington, Seattle, Washington.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Adam</LastName><ForeName>Margaret P</ForeName><Initials>MP</Initials><AffiliationInfo><Affiliation>Division of Genetic Medicine, Department of Pediatrics, University of Washington & Seattle Children's Hospital, Seattle, Washington.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Byers</LastName><ForeName>Peter H</ForeName><Initials>PH</Initials><AffiliationInfo><Affiliation>Department of Pathology, University of Washington, Seattle, Washington.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Medicine, University of Washington, Seattle, Washington.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mefford</LastName><ForeName>Heather C</ForeName><Initials>HC</Initials><AffiliationInfo><Affiliation>Division of Genetic Medicine, Department of Pediatrics, University of Washington & Seattle Children's Hospital, Seattle, Washington.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>T32 GM007454</GrantID><Acronym>GM</Acronym><Agency>NIGMS NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D002363">Case Reports</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2015</Year><Month>06</Month><Day>18</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Am J Med Genet A</MedlineTA><NlmUniqueID>101235741</NlmUniqueID><ISSNLinking>1552-4825</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>EC 2.4.1.135</RegistryNumber><NameOfSubstance UI="C000594393">B3GAT3 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.4.1.17</RegistryNumber><NameOfSubstance UI="D014453">Glucuronosyltransferase</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>Nat Methods. 2010 Apr;7(4):248-9</RefSource><PMID Version="1">20354512</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Biol Chem. 1998 Mar 20;273(12):6615-8</RefSource><PMID Version="1">9506957</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Biol Chem. 2005 Jan 14;280(2):1417-25</RefSource><PMID Version="1">15522873</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Am J Med Genet A. 2014 Jun;164A(6):1580-6</RefSource><PMID Version="1">24668659</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Am J Hum Genet. 2014 Mar 6;94(3):405-14</RefSource><PMID Version="1">24581741</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Eur J Hum Genet. 2015 Jan;23(1):49-53</RefSource><PMID Version="1">24755949</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nature. 2007 Apr 26;446(7139):1030-7</RefSource><PMID Version="1">17460664</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Biol Chem. 2007 Feb 23;282(8):5201-6</RefSource><PMID Version="1">17189265</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nat Rev Genet. 2006 Jul;7(7):537-51</RefSource><PMID Version="1">16755287</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nat Rev Mol Cell Biol. 2005 Jul;6(7):530-41</RefSource><PMID Version="1">16072037</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Am J Med Genet A. 2004 Jul 1;128A(1):39-45</RefSource><PMID Version="1">15211654</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Am J Hum Genet. 1987 Sep;41(3):436-53</RefSource><PMID Version="1">3631078</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Am J Hum Genet. 2011 Jul 15;89(1):15-27</RefSource><PMID Version="1">21763480</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Am J Med Genet A. 2013 Oct;161A(10):2519-27</RefSource><PMID Version="1">23956117</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Am J Hum Genet. 2013 Jun 6;92(6):927-34</RefSource><PMID Version="1">23664117</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Am J Hum Genet. 2013 Jun 6;92(6):935-45</RefSource><PMID Version="1">23664118</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Hum Genet. 2014 Jan;133(1):29-39</RefSource><PMID Version="1">23982343</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Annu Rev Biochem. 2004;73:491-537</RefSource><PMID Version="1">15189151</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Curr Opin Struct Biol. 2003 Oct;13(5):612-20</RefSource><PMID Version="1">14568617</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Annu Rev Biochem. 1999;68:729-77</RefSource><PMID Version="1">10872465</PMID></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName UI="D000069076" MajorTopicYN="N">Fractures, Multiple</DescriptorName><QualifierName UI="Q000000981" MajorTopicYN="N">diagnostic imaging</QualifierName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005820" MajorTopicYN="N">Genetic Testing</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014453" MajorTopicYN="N">Glucuronosyltransferase</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006720" MajorTopicYN="N">Homozygote</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007223" MajorTopicYN="N">Infant</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007231" MajorTopicYN="N">Infant, Newborn</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009154" MajorTopicYN="N">Mutation</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010641" MajorTopicYN="N">Phenotype</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011859" MajorTopicYN="N">Radiography</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013577" MajorTopicYN="N">Syndrome</DescriptorName></MeshHeading></MeshHeadingList><OtherID Source="NLM">NIHMS734079</OtherID><OtherID Source="NLM">PMC4654953</OtherID><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">B3GAT3</Keyword><Keyword MajorTopicYN="N">congenital disorder of glycosylation</Keyword><Keyword MajorTopicYN="N">linkeropathy</Keyword><Keyword MajorTopicYN="N">multiple fractures</Keyword><Keyword MajorTopicYN="N">proteoglycan disorder</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2015</Year><Month>04</Month><Day>01</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2015</Year><Month>06</Month><Day>03</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2015</Year><Month>6</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2015</Year><Month>6</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2016</Year><Month>8</Month><Day>30</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">26086840</ArticleId><ArticleId IdType="doi">10.1002/ajmg.a.37209</ArticleId><ArticleId IdType="pmc">PMC4654953</ArticleId><ArticleId IdType="mid">NIHMS734079</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/LymphedemaV1/Data/PubMed/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000E31 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/PubMed/Corpus/biblio.hfd -nk 000E31 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= LymphedemaV1
|flux= PubMed
|étape= Corpus
|type= RBID
|clé= pubmed:26086840
|texte= A homozygous B3GAT3 mutation causes a severe syndrome with multiple fractures, expanding the phenotype of linkeropathy syndromes.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/PubMed/Corpus/RBID.i -Sk "pubmed:26086840" \
| HfdSelect -Kh $EXPLOR_AREA/Data/PubMed/Corpus/biblio.hfd \
| NlmPubMed2Wicri -a LymphedemaV1
| This area was generated with Dilib version V0.6.31. |  |