Functional characterization of GATA3 mutations causing the hypoparathyroidism-deafness-renal (HDR) dysplasia syndrome : Insight into mechanisms of DNA binding by the GATA3 transcription factor
Identifieur interne : 003D06 ( PascalFrancis/Corpus ); précédent : 003D05; suivant : 003D07Functional characterization of GATA3 mutations causing the hypoparathyroidism-deafness-renal (HDR) dysplasia syndrome : Insight into mechanisms of DNA binding by the GATA3 transcription factor
Auteurs : Asif Ali ; Paul T. Christie ; Irina V. Grigorieva ; Brian Harding ; Hilde Van Esch ; S. Faisal Ahmed ; Maria Bitner-Glindzicz ; Eberhard Blind ; Catherine Bloch ; Patricia Christin ; Peter Clayton ; Jozef Gecz ; Brigitte Gilbert-Dussardier ; Encarna Guillen-Navarro ; Anna Hackett ; Isil Halac ; Geoffrey N. Hendy ; Fiona Lalloo ; Christoph J. Mache ; Zulf Mughal ; Albert C. M. Ong ; Choni Rinat ; Nicholas Shaw ; Sarah F. Smithson ; John Tolmie ; Jacques Weill ; M. Andrew Nesbit ; Rajesh V. ThakkerSource :
- Human molecular genetics : (Print) [ 0964-6906 ] ; 2007.
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Abstract
The hypoparathyroidism-deafness-renal (HDR) dysplasia syndrome is an autosomal dominant disorder caused by mutations of the dual zinc finger transcription factor, GATA3. We investigated 21 HDR probands and 14 patients with isolated hypoparathyroidism for GATA3 abnormalities. Thirteen different heterozygous germline mutations were identified in patients with HDR. These consisted of three nonsense mutations, six frameshifting deletions, two frameshifting insertions, one missense (Leu348Arg) mutation and one acceptor splice site mutation. The splice site mutation was demonstrated to cause a pre-mRNA processing abnormality leading to the use of an alternative acceptor site 8 bp downstream of the normal site, resulting in a frame-shift and prematurely terminated protein. Electrophoretic mobility shift assays (EMSAs) revealed three classes of GATA3 mutations: those that lead to a loss of DNA binding which represent over 90% of all mutations, and involved a loss of the carboxy-terminal zinc finger; those that resulted in a reduced DNA-binding affinity; and those (e.g. Leu348Arg) that did not alter DNA binding or the affinity but likely altered the conformational change that occurs during binding in the DNA major groove as predicted by a three-dimensional modeling. These results elucidate further the molecular mechanisms underlying the altered functions of mutants of this zinc finger transcription factor and their role in causing this developmental anomaly. No mutations were identified in patients with isolated hypoparathyroidism, thereby indicating that GATA3 abnormalities are more likely to result in two or more of the phenotypic features of the HDR syndrome and not in one, such as isolated hypoparathyroidism.
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Format Inist (serveur)
| NO : | PASCAL 07-0187922 INIST |
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| ET : | Functional characterization of GATA3 mutations causing the hypoparathyroidism-deafness-renal (HDR) dysplasia syndrome : Insight into mechanisms of DNA binding by the GATA3 transcription factor |
| AU : | ALI (Asif); CHRISTIE (Paul T.); GRIGORIEVA (Irina V.); HARDING (Brian); VAN ESCH (Hilde); FAISAL AHMED (S.); BITNER-GLINDZICZ (Maria); BLIND (Eberhard); BLOCH (Catherine); CHRISTIN (Patricia); CLAYTON (Peter); GECZ (Jozef); GILBERT-DUSSARDIER (Brigitte); GUILLEN-NAVARRO (Encarna); HACKETT (Anna); HALAC (Isil); HENDY (Geoffrey N.); LALLOO (Fiona); MACHE (Christoph J.); MUGHAL (Zulf); ONG (Albert C. M.); RINAT (Choni); SHAW (Nicholas); SMITHSON (Sarah F.); TOLMIE (John); WEILL (Jacques); NESBIT (M. Andrew); THAKKER (Rajesh V.) |
| AF : | Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, Churchill Hospital/Headington, Oxford OX3 7LJ/Royaume-Uni (1 aut., 2 aut., 3 aut., 4 aut., 27 aut., 28 aut.); Department of Clinical Genetics, Centre for Human Genetics, University Hospital Leuven, Herestraat 49/3000 Leuven/Belgique (5 aut.); Royal Hospital for Sick Children, Dalnair Street/Glasgow G3 8SJ/Royaume-Uni (6 aut.); Clinical and Molecular Genetics Unit, Institute for Child Health/London WC1 N1EH/Royaume-Uni (7 aut.); Department of Medicine, Endocrinology, University of Würtzburg, Josef-Schneider-Str. 2/97080 Würtzburg/Allemagne (8 aut.); Hopital Lenval, 57 Av. De la Californie 06 200/Nice/France (9 aut.); Service de Gènètique Mèdicale, CHU la Milètrie, B.P. 577/86021 Poitiers/France (10 aut., 13 aut.); Royal Manchester Childrens Hospital, Hospital Road, Pendlebury/Manchester M27 4HA/Royaume-Uni (11 aut.); Department of Genetic Medicine, Women's and Children's Hospital, 72 King William Road, North Adelaide/SA 5006, Adelaide/Australie (12 aut.); Unidad de Genetica Medica, Hospital Universitario Virgen de la Arraxaca, Ctra Madrid-Cartagena/El Palmar 30120/Espagne (14 aut.); Hunter Genetics, PO Box 84/Waratah, New South Wales 2298/Australie (15 aut.) |
| DT : | Publication en série; Niveau analytique |
| SO : | Human molecular genetics : (Print); ISSN 0964-6906; Royaume-Uni; Da. 2007; Vol. 16; No. 3; Pp. 265-275; Bibl. 40 ref. |
| LA : | Anglais |
| EA : | The hypoparathyroidism-deafness-renal (HDR) dysplasia syndrome is an autosomal dominant disorder caused by mutations of the dual zinc finger transcription factor, GATA3. We investigated 21 HDR probands and 14 patients with isolated hypoparathyroidism for GATA3 abnormalities. Thirteen different heterozygous germline mutations were identified in patients with HDR. These consisted of three nonsense mutations, six frameshifting deletions, two frameshifting insertions, one missense (Leu348Arg) mutation and one acceptor splice site mutation. The splice site mutation was demonstrated to cause a pre-mRNA processing abnormality leading to the use of an alternative acceptor site 8 bp downstream of the normal site, resulting in a frame-shift and prematurely terminated protein. Electrophoretic mobility shift assays (EMSAs) revealed three classes of GATA3 mutations: those that lead to a loss of DNA binding which represent over 90% of all mutations, and involved a loss of the carboxy-terminal zinc finger; those that resulted in a reduced DNA-binding affinity; and those (e.g. Leu348Arg) that did not alter DNA binding or the affinity but likely altered the conformational change that occurs during binding in the DNA major groove as predicted by a three-dimensional modeling. These results elucidate further the molecular mechanisms underlying the altered functions of mutants of this zinc finger transcription factor and their role in causing this developmental anomaly. No mutations were identified in patients with isolated hypoparathyroidism, thereby indicating that GATA3 abnormalities are more likely to result in two or more of the phenotypic features of the HDR syndrome and not in one, such as isolated hypoparathyroidism. |
| CC : | 002A04; 002A07; 002B21D01 |
| FD : | Caractérisation; Mutation; Dysplasie rénale; Syndrome; Mécanisme; DNA; Facteur transcription; Génétique; Hypoparathyroïdie; Surdité |
| FG : | Parathyroïde pathologie; ORL pathologie; Trouble audition; Appareil urinaire pathologie; Maladie congénitale; Malformation; Endocrinopathie; Rein pathologie |
| ED : | Characterization; Mutation; Renal dysplasia; Syndrome; Mechanism; DNA; Transcription factor; Genetics; Hypoparathyroidism; Hearing loss |
| EG : | Parathyroid diseases; ENT disease; Auditory disorder; Urinary system disease; Congenital disease; Malformation; Endocrinopathy; Kidney disease |
| SD : | Caracterización; Mutación; Displasia renal; Síndrome; Mecanismo; DNA; Factor transcripción; Genética; Hipoparatiroidismo; Sordera |
| LO : | INIST-22540.354000143293050030 |
| ID : | 07-0187922 |
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Pascal:07-0187922Le document en format XML
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Faisal Ahmed</name><affiliation><inist:fA14 i1="03"><s1>Royal Hospital for Sick Children, Dalnair Street</s1><s2>Glasgow G3 8SJ</s2><s3>GBR</s3><sZ>6 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Bitner Glindzicz, Maria" sort="Bitner Glindzicz, Maria" uniqKey="Bitner Glindzicz M" first="Maria" last="Bitner-Glindzicz">Maria Bitner-Glindzicz</name><affiliation><inist:fA14 i1="04"><s1>Clinical and Molecular Genetics Unit, Institute for Child Health</s1><s2>London WC1 N1EH</s2><s3>GBR</s3><sZ>7 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Blind, Eberhard" sort="Blind, Eberhard" uniqKey="Blind E" first="Eberhard" last="Blind">Eberhard Blind</name><affiliation><inist:fA14 i1="05"><s1>Department of Medicine, Endocrinology, University of Würtzburg, Josef-Schneider-Str. 2</s1><s2>97080 Würtzburg</s2><s3>DEU</s3><sZ>8 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Bloch, Catherine" sort="Bloch, Catherine" uniqKey="Bloch C" first="Catherine" last="Bloch">Catherine Bloch</name><affiliation><inist:fA14 i1="06"><s1>Hopital Lenval, 57 Av. De la Californie 06 200</s1><s2>Nice</s2><s3>FRA</s3><sZ>9 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Christin, Patricia" sort="Christin, Patricia" uniqKey="Christin P" first="Patricia" last="Christin">Patricia Christin</name><affiliation><inist:fA14 i1="07"><s1>Service de Gènètique Mèdicale, CHU la Milètrie, B.P. 577</s1><s2>86021 Poitiers</s2><s3>FRA</s3><sZ>10 aut.</sZ><sZ>13 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Clayton, Peter" sort="Clayton, Peter" uniqKey="Clayton P" first="Peter" last="Clayton">Peter Clayton</name><affiliation><inist:fA14 i1="08"><s1>Royal Manchester Childrens Hospital, Hospital Road, Pendlebury</s1><s2>Manchester M27 4HA</s2><s3>GBR</s3><sZ>11 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Gecz, Jozef" sort="Gecz, Jozef" uniqKey="Gecz J" first="Jozef" last="Gecz">Jozef Gecz</name><affiliation><inist:fA14 i1="09"><s1>Department of Genetic Medicine, Women's and Children's Hospital, 72 King William Road, North Adelaide</s1><s2>SA 5006, Adelaide</s2><s3>AUS</s3><sZ>12 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Gilbert Dussardier, Brigitte" sort="Gilbert Dussardier, Brigitte" uniqKey="Gilbert Dussardier B" first="Brigitte" last="Gilbert-Dussardier">Brigitte Gilbert-Dussardier</name><affiliation><inist:fA14 i1="07"><s1>Service de Gènètique Mèdicale, CHU la Milètrie, B.P. 577</s1><s2>86021 Poitiers</s2><s3>FRA</s3><sZ>10 aut.</sZ><sZ>13 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Guillen Navarro, Encarna" sort="Guillen Navarro, Encarna" uniqKey="Guillen Navarro E" first="Encarna" last="Guillen-Navarro">Encarna Guillen-Navarro</name><affiliation><inist:fA14 i1="10"><s1>Unidad de Genetica Medica, Hospital Universitario Virgen de la Arraxaca, Ctra Madrid-Cartagena</s1><s2>El Palmar 30120</s2><s3>ESP</s3><sZ>14 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Hackett, Anna" sort="Hackett, Anna" uniqKey="Hackett A" first="Anna" last="Hackett">Anna Hackett</name><affiliation><inist:fA14 i1="11"><s1>Hunter Genetics, PO Box 84</s1><s2>Waratah, New South Wales 2298</s2><s3>AUS</s3><sZ>15 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Halac, Isil" sort="Halac, Isil" uniqKey="Halac I" first="Isil" last="Halac">Isil Halac</name></author><author><name sortKey="Hendy, Geoffrey N" sort="Hendy, Geoffrey N" uniqKey="Hendy G" first="Geoffrey N." last="Hendy">Geoffrey N. Hendy</name></author><author><name sortKey="Lalloo, Fiona" sort="Lalloo, Fiona" uniqKey="Lalloo F" first="Fiona" last="Lalloo">Fiona Lalloo</name></author><author><name sortKey="Mache, Christoph J" sort="Mache, Christoph J" uniqKey="Mache C" first="Christoph J." last="Mache">Christoph J. Mache</name></author><author><name sortKey="Mughal, Zulf" sort="Mughal, Zulf" uniqKey="Mughal Z" first="Zulf" last="Mughal">Zulf Mughal</name></author><author><name sortKey="Ong, Albert C M" sort="Ong, Albert C M" uniqKey="Ong A" first="Albert C. M." last="Ong">Albert C. M. Ong</name></author><author><name sortKey="Rinat, Choni" sort="Rinat, Choni" uniqKey="Rinat C" first="Choni" last="Rinat">Choni Rinat</name></author><author><name sortKey="Shaw, Nicholas" sort="Shaw, Nicholas" uniqKey="Shaw N" first="Nicholas" last="Shaw">Nicholas Shaw</name></author><author><name sortKey="Smithson, Sarah F" sort="Smithson, Sarah F" uniqKey="Smithson S" first="Sarah F." last="Smithson">Sarah F. Smithson</name></author><author><name sortKey="Tolmie, John" sort="Tolmie, John" uniqKey="Tolmie J" first="John" last="Tolmie">John Tolmie</name></author><author><name sortKey="Weill, Jacques" sort="Weill, Jacques" uniqKey="Weill J" first="Jacques" last="Weill">Jacques Weill</name></author><author><name sortKey="Nesbit, M Andrew" sort="Nesbit, M Andrew" uniqKey="Nesbit M" first="M. Andrew" last="Nesbit">M. Andrew Nesbit</name><affiliation><inist:fA14 i1="01"><s1>Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, Churchill Hospital</s1><s2>Headington, Oxford OX3 7LJ</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>27 aut.</sZ><sZ>28 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Thakker, Rajesh V" sort="Thakker, Rajesh V" uniqKey="Thakker R" first="Rajesh V." last="Thakker">Rajesh V. Thakker</name><affiliation><inist:fA14 i1="01"><s1>Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, Churchill Hospital</s1><s2>Headington, Oxford OX3 7LJ</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>27 aut.</sZ><sZ>28 aut.</sZ></inist:fA14></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">07-0187922</idno><date when="2007">2007</date><idno type="stanalyst">PASCAL 07-0187922 INIST</idno><idno type="RBID">Pascal:07-0187922</idno><idno type="wicri:Area/PascalFrancis/Corpus">003D06</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Functional characterization of GATA3 mutations causing the hypoparathyroidism-deafness-renal (HDR) dysplasia syndrome : Insight into mechanisms of DNA binding by the GATA3 transcription factor</title><author><name sortKey="Ali, Asif" sort="Ali, Asif" uniqKey="Ali A" first="Asif" last="Ali">Asif Ali</name><affiliation><inist:fA14 i1="01"><s1>Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, Churchill Hospital</s1><s2>Headington, Oxford OX3 7LJ</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>27 aut.</sZ><sZ>28 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Christie, Paul T" sort="Christie, Paul T" uniqKey="Christie P" first="Paul T." last="Christie">Paul T. Christie</name><affiliation><inist:fA14 i1="01"><s1>Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, Churchill Hospital</s1><s2>Headington, Oxford OX3 7LJ</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>27 aut.</sZ><sZ>28 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Grigorieva, Irina V" sort="Grigorieva, Irina V" uniqKey="Grigorieva I" first="Irina V." last="Grigorieva">Irina V. Grigorieva</name><affiliation><inist:fA14 i1="01"><s1>Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, Churchill Hospital</s1><s2>Headington, Oxford OX3 7LJ</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>27 aut.</sZ><sZ>28 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Harding, Brian" sort="Harding, Brian" uniqKey="Harding B" first="Brian" last="Harding">Brian Harding</name><affiliation><inist:fA14 i1="01"><s1>Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, Churchill Hospital</s1><s2>Headington, Oxford OX3 7LJ</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>27 aut.</sZ><sZ>28 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Van Esch, Hilde" sort="Van Esch, Hilde" uniqKey="Van Esch H" first="Hilde" last="Van Esch">Hilde Van Esch</name><affiliation><inist:fA14 i1="02"><s1>Department of Clinical Genetics, Centre for Human Genetics, University Hospital Leuven, Herestraat 49</s1><s2>3000 Leuven</s2><s3>BEL</s3><sZ>5 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Faisal Ahmed, S" sort="Faisal Ahmed, S" uniqKey="Faisal Ahmed S" first="S." last="Faisal Ahmed">S. Faisal Ahmed</name><affiliation><inist:fA14 i1="03"><s1>Royal Hospital for Sick Children, Dalnair Street</s1><s2>Glasgow G3 8SJ</s2><s3>GBR</s3><sZ>6 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Bitner Glindzicz, Maria" sort="Bitner Glindzicz, Maria" uniqKey="Bitner Glindzicz M" first="Maria" last="Bitner-Glindzicz">Maria Bitner-Glindzicz</name><affiliation><inist:fA14 i1="04"><s1>Clinical and Molecular Genetics Unit, Institute for Child Health</s1><s2>London WC1 N1EH</s2><s3>GBR</s3><sZ>7 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Blind, Eberhard" sort="Blind, Eberhard" uniqKey="Blind E" first="Eberhard" last="Blind">Eberhard Blind</name><affiliation><inist:fA14 i1="05"><s1>Department of Medicine, Endocrinology, University of Würtzburg, Josef-Schneider-Str. 2</s1><s2>97080 Würtzburg</s2><s3>DEU</s3><sZ>8 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Bloch, Catherine" sort="Bloch, Catherine" uniqKey="Bloch C" first="Catherine" last="Bloch">Catherine Bloch</name><affiliation><inist:fA14 i1="06"><s1>Hopital Lenval, 57 Av. De la Californie 06 200</s1><s2>Nice</s2><s3>FRA</s3><sZ>9 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Christin, Patricia" sort="Christin, Patricia" uniqKey="Christin P" first="Patricia" last="Christin">Patricia Christin</name><affiliation><inist:fA14 i1="07"><s1>Service de Gènètique Mèdicale, CHU la Milètrie, B.P. 577</s1><s2>86021 Poitiers</s2><s3>FRA</s3><sZ>10 aut.</sZ><sZ>13 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Clayton, Peter" sort="Clayton, Peter" uniqKey="Clayton P" first="Peter" last="Clayton">Peter Clayton</name><affiliation><inist:fA14 i1="08"><s1>Royal Manchester Childrens Hospital, Hospital Road, Pendlebury</s1><s2>Manchester M27 4HA</s2><s3>GBR</s3><sZ>11 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Gecz, Jozef" sort="Gecz, Jozef" uniqKey="Gecz J" first="Jozef" last="Gecz">Jozef Gecz</name><affiliation><inist:fA14 i1="09"><s1>Department of Genetic Medicine, Women's and Children's Hospital, 72 King William Road, North Adelaide</s1><s2>SA 5006, Adelaide</s2><s3>AUS</s3><sZ>12 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Gilbert Dussardier, Brigitte" sort="Gilbert Dussardier, Brigitte" uniqKey="Gilbert Dussardier B" first="Brigitte" last="Gilbert-Dussardier">Brigitte Gilbert-Dussardier</name><affiliation><inist:fA14 i1="07"><s1>Service de Gènètique Mèdicale, CHU la Milètrie, B.P. 577</s1><s2>86021 Poitiers</s2><s3>FRA</s3><sZ>10 aut.</sZ><sZ>13 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Guillen Navarro, Encarna" sort="Guillen Navarro, Encarna" uniqKey="Guillen Navarro E" first="Encarna" last="Guillen-Navarro">Encarna Guillen-Navarro</name><affiliation><inist:fA14 i1="10"><s1>Unidad de Genetica Medica, Hospital Universitario Virgen de la Arraxaca, Ctra Madrid-Cartagena</s1><s2>El Palmar 30120</s2><s3>ESP</s3><sZ>14 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Hackett, Anna" sort="Hackett, Anna" uniqKey="Hackett A" first="Anna" last="Hackett">Anna Hackett</name><affiliation><inist:fA14 i1="11"><s1>Hunter Genetics, PO Box 84</s1><s2>Waratah, New South Wales 2298</s2><s3>AUS</s3><sZ>15 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Halac, Isil" sort="Halac, Isil" uniqKey="Halac I" first="Isil" last="Halac">Isil Halac</name></author><author><name sortKey="Hendy, Geoffrey N" sort="Hendy, Geoffrey N" uniqKey="Hendy G" first="Geoffrey N." last="Hendy">Geoffrey N. Hendy</name></author><author><name sortKey="Lalloo, Fiona" sort="Lalloo, Fiona" uniqKey="Lalloo F" first="Fiona" last="Lalloo">Fiona Lalloo</name></author><author><name sortKey="Mache, Christoph J" sort="Mache, Christoph J" uniqKey="Mache C" first="Christoph J." last="Mache">Christoph J. Mache</name></author><author><name sortKey="Mughal, Zulf" sort="Mughal, Zulf" uniqKey="Mughal Z" first="Zulf" last="Mughal">Zulf Mughal</name></author><author><name sortKey="Ong, Albert C M" sort="Ong, Albert C M" uniqKey="Ong A" first="Albert C. M." last="Ong">Albert C. M. Ong</name></author><author><name sortKey="Rinat, Choni" sort="Rinat, Choni" uniqKey="Rinat C" first="Choni" last="Rinat">Choni Rinat</name></author><author><name sortKey="Shaw, Nicholas" sort="Shaw, Nicholas" uniqKey="Shaw N" first="Nicholas" last="Shaw">Nicholas Shaw</name></author><author><name sortKey="Smithson, Sarah F" sort="Smithson, Sarah F" uniqKey="Smithson S" first="Sarah F." last="Smithson">Sarah F. Smithson</name></author><author><name sortKey="Tolmie, John" sort="Tolmie, John" uniqKey="Tolmie J" first="John" last="Tolmie">John Tolmie</name></author><author><name sortKey="Weill, Jacques" sort="Weill, Jacques" uniqKey="Weill J" first="Jacques" last="Weill">Jacques Weill</name></author><author><name sortKey="Nesbit, M Andrew" sort="Nesbit, M Andrew" uniqKey="Nesbit M" first="M. Andrew" last="Nesbit">M. Andrew Nesbit</name><affiliation><inist:fA14 i1="01"><s1>Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, Churchill Hospital</s1><s2>Headington, Oxford OX3 7LJ</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>27 aut.</sZ><sZ>28 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Thakker, Rajesh V" sort="Thakker, Rajesh V" uniqKey="Thakker R" first="Rajesh V." last="Thakker">Rajesh V. Thakker</name><affiliation><inist:fA14 i1="01"><s1>Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, Churchill Hospital</s1><s2>Headington, Oxford OX3 7LJ</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>27 aut.</sZ><sZ>28 aut.</sZ></inist:fA14></affiliation></author></analytic><series><title level="j" type="main">Human molecular genetics : (Print)</title><title level="j" type="abbreviated">Hum. mol. genet. : (Print)</title><idno type="ISSN">0964-6906</idno><imprint><date when="2007">2007</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Human molecular genetics : (Print)</title><title level="j" type="abbreviated">Hum. mol. genet. : (Print)</title><idno type="ISSN">0964-6906</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Characterization</term><term>DNA</term><term>Genetics</term><term>Hearing loss</term><term>Hypoparathyroidism</term><term>Mechanism</term><term>Mutation</term><term>Renal dysplasia</term><term>Syndrome</term><term>Transcription factor</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Caractérisation</term><term>Mutation</term><term>Dysplasie rénale</term><term>Syndrome</term><term>Mécanisme</term><term>DNA</term><term>Facteur transcription</term><term>Génétique</term><term>Hypoparathyroïdie</term><term>Surdité</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The hypoparathyroidism-deafness-renal (HDR) dysplasia syndrome is an autosomal dominant disorder caused by mutations of the dual zinc finger transcription factor, GATA3. We investigated 21 HDR probands and 14 patients with isolated hypoparathyroidism for GATA3 abnormalities. Thirteen different heterozygous germline mutations were identified in patients with HDR. These consisted of three nonsense mutations, six frameshifting deletions, two frameshifting insertions, one missense (Leu348Arg) mutation and one acceptor splice site mutation. The splice site mutation was demonstrated to cause a pre-mRNA processing abnormality leading to the use of an alternative acceptor site 8 bp downstream of the normal site, resulting in a frame-shift and prematurely terminated protein. Electrophoretic mobility shift assays (EMSAs) revealed three classes of GATA3 mutations: those that lead to a loss of DNA binding which represent over 90% of all mutations, and involved a loss of the carboxy-terminal zinc finger; those that resulted in a reduced DNA-binding affinity; and those (e.g. Leu348Arg) that did not alter DNA binding or the affinity but likely altered the conformational change that occurs during binding in the DNA major groove as predicted by a three-dimensional modeling. These results elucidate further the molecular mechanisms underlying the altered functions of mutants of this zinc finger transcription factor and their role in causing this developmental anomaly. No mutations were identified in patients with isolated hypoparathyroidism, thereby indicating that GATA3 abnormalities are more likely to result in two or more of the phenotypic features of the HDR syndrome and not in one, such as isolated hypoparathyroidism.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0964-6906</s0></fA01><fA03 i2="1"><s0>Hum. mol. genet. : (Print)</s0></fA03><fA05><s2>16</s2></fA05><fA06><s2>3</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Functional characterization of GATA3 mutations causing the hypoparathyroidism-deafness-renal (HDR) dysplasia syndrome : Insight into mechanisms of DNA binding by the GATA3 transcription factor</s1></fA08><fA11 i1="01" i2="1"><s1>ALI (Asif)</s1></fA11><fA11 i1="02" i2="1"><s1>CHRISTIE (Paul T.)</s1></fA11><fA11 i1="03" i2="1"><s1>GRIGORIEVA (Irina V.)</s1></fA11><fA11 i1="04" i2="1"><s1>HARDING (Brian)</s1></fA11><fA11 i1="05" i2="1"><s1>VAN ESCH (Hilde)</s1></fA11><fA11 i1="06" i2="1"><s1>FAISAL AHMED (S.)</s1></fA11><fA11 i1="07" i2="1"><s1>BITNER-GLINDZICZ (Maria)</s1></fA11><fA11 i1="08" i2="1"><s1>BLIND (Eberhard)</s1></fA11><fA11 i1="09" i2="1"><s1>BLOCH (Catherine)</s1></fA11><fA11 i1="10" i2="1"><s1>CHRISTIN (Patricia)</s1></fA11><fA11 i1="11" i2="1"><s1>CLAYTON (Peter)</s1></fA11><fA11 i1="12" i2="1"><s1>GECZ (Jozef)</s1></fA11><fA11 i1="13" i2="1"><s1>GILBERT-DUSSARDIER (Brigitte)</s1></fA11><fA11 i1="14" i2="1"><s1>GUILLEN-NAVARRO (Encarna)</s1></fA11><fA11 i1="15" i2="1"><s1>HACKETT (Anna)</s1></fA11><fA11 i1="16" i2="1"><s1>HALAC (Isil)</s1></fA11><fA11 i1="17" i2="1"><s1>HENDY (Geoffrey N.)</s1></fA11><fA11 i1="18" i2="1"><s1>LALLOO (Fiona)</s1></fA11><fA11 i1="19" i2="1"><s1>MACHE (Christoph J.)</s1></fA11><fA11 i1="20" i2="1"><s1>MUGHAL (Zulf)</s1></fA11><fA11 i1="21" i2="1"><s1>ONG (Albert C. M.)</s1></fA11><fA11 i1="22" i2="1"><s1>RINAT (Choni)</s1></fA11><fA11 i1="23" i2="1"><s1>SHAW (Nicholas)</s1></fA11><fA11 i1="24" i2="1"><s1>SMITHSON (Sarah F.)</s1></fA11><fA11 i1="25" i2="1"><s1>TOLMIE (John)</s1></fA11><fA11 i1="26" i2="1"><s1>WEILL (Jacques)</s1></fA11><fA11 i1="27" i2="1"><s1>NESBIT (M. Andrew)</s1></fA11><fA11 i1="28" i2="1"><s1>THAKKER (Rajesh V.)</s1></fA11><fA14 i1="01"><s1>Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, Churchill Hospital</s1><s2>Headington, Oxford OX3 7LJ</s2><s3>GBR</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>27 aut.</sZ><sZ>28 aut.</sZ></fA14><fA14 i1="02"><s1>Department of Clinical Genetics, Centre for Human Genetics, University Hospital Leuven, Herestraat 49</s1><s2>3000 Leuven</s2><s3>BEL</s3><sZ>5 aut.</sZ></fA14><fA14 i1="03"><s1>Royal Hospital for Sick Children, Dalnair Street</s1><s2>Glasgow G3 8SJ</s2><s3>GBR</s3><sZ>6 aut.</sZ></fA14><fA14 i1="04"><s1>Clinical and Molecular Genetics Unit, Institute for Child Health</s1><s2>London WC1 N1EH</s2><s3>GBR</s3><sZ>7 aut.</sZ></fA14><fA14 i1="05"><s1>Department of Medicine, Endocrinology, University of Würtzburg, Josef-Schneider-Str. 2</s1><s2>97080 Würtzburg</s2><s3>DEU</s3><sZ>8 aut.</sZ></fA14><fA14 i1="06"><s1>Hopital Lenval, 57 Av. De la Californie 06 200</s1><s2>Nice</s2><s3>FRA</s3><sZ>9 aut.</sZ></fA14><fA14 i1="07"><s1>Service de Gènètique Mèdicale, CHU la Milètrie, B.P. 577</s1><s2>86021 Poitiers</s2><s3>FRA</s3><sZ>10 aut.</sZ><sZ>13 aut.</sZ></fA14><fA14 i1="08"><s1>Royal Manchester Childrens Hospital, Hospital Road, Pendlebury</s1><s2>Manchester M27 4HA</s2><s3>GBR</s3><sZ>11 aut.</sZ></fA14><fA14 i1="09"><s1>Department of Genetic Medicine, Women's and Children's Hospital, 72 King William Road, North Adelaide</s1><s2>SA 5006, Adelaide</s2><s3>AUS</s3><sZ>12 aut.</sZ></fA14><fA14 i1="10"><s1>Unidad de Genetica Medica, Hospital Universitario Virgen de la Arraxaca, Ctra Madrid-Cartagena</s1><s2>El Palmar 30120</s2><s3>ESP</s3><sZ>14 aut.</sZ></fA14><fA14 i1="11"><s1>Hunter Genetics, PO Box 84</s1><s2>Waratah, New South Wales 2298</s2><s3>AUS</s3><sZ>15 aut.</sZ></fA14><fA20><s1>265-275</s1></fA20><fA21><s1>2007</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>22540</s2><s5>354000143293050030</s5></fA43><fA44><s0>0000</s0><s1>© 2007 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>40 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>07-0187922</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Human molecular genetics : (Print)</s0></fA64><fA66 i1="01"><s0>GBR</s0></fA66><fC01 i1="01" l="ENG"><s0>The hypoparathyroidism-deafness-renal (HDR) dysplasia syndrome is an autosomal dominant disorder caused by mutations of the dual zinc finger transcription factor, GATA3. We investigated 21 HDR probands and 14 patients with isolated hypoparathyroidism for GATA3 abnormalities. Thirteen different heterozygous germline mutations were identified in patients with HDR. These consisted of three nonsense mutations, six frameshifting deletions, two frameshifting insertions, one missense (Leu348Arg) mutation and one acceptor splice site mutation. The splice site mutation was demonstrated to cause a pre-mRNA processing abnormality leading to the use of an alternative acceptor site 8 bp downstream of the normal site, resulting in a frame-shift and prematurely terminated protein. Electrophoretic mobility shift assays (EMSAs) revealed three classes of GATA3 mutations: those that lead to a loss of DNA binding which represent over 90% of all mutations, and involved a loss of the carboxy-terminal zinc finger; those that resulted in a reduced DNA-binding affinity; and those (e.g. Leu348Arg) that did not alter DNA binding or the affinity but likely altered the conformational change that occurs during binding in the DNA major groove as predicted by a three-dimensional modeling. These results elucidate further the molecular mechanisms underlying the altered functions of mutants of this zinc finger transcription factor and their role in causing this developmental anomaly. No mutations were identified in patients with isolated hypoparathyroidism, thereby indicating that GATA3 abnormalities are more likely to result in two or more of the phenotypic features of the HDR syndrome and not in one, such as isolated hypoparathyroidism.</s0></fC01><fC02 i1="01" i2="X"><s0>002A04</s0></fC02><fC02 i1="02" i2="X"><s0>002A07</s0></fC02><fC02 i1="03" i2="X"><s0>002B21D01</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Caractérisation</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Characterization</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Caracterización</s0><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Mutation</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Mutation</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Mutación</s0><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Dysplasie rénale</s0><s2>NM</s2><s5>03</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Renal dysplasia</s0><s2>NM</s2><s5>03</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Displasia renal</s0><s2>NM</s2><s5>03</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Syndrome</s0><s5>04</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Syndrome</s0><s5>04</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Síndrome</s0><s5>04</s5></fC03><fC03 i1="05" i2="X" l="FRE"><s0>Mécanisme</s0><s5>05</s5></fC03><fC03 i1="05" i2="X" l="ENG"><s0>Mechanism</s0><s5>05</s5></fC03><fC03 i1="05" i2="X" l="SPA"><s0>Mecanismo</s0><s5>05</s5></fC03><fC03 i1="06" i2="X" l="FRE"><s0>DNA</s0><s5>06</s5></fC03><fC03 i1="06" i2="X" l="ENG"><s0>DNA</s0><s5>06</s5></fC03><fC03 i1="06" i2="X" l="SPA"><s0>DNA</s0><s5>06</s5></fC03><fC03 i1="07" i2="X" l="FRE"><s0>Facteur transcription</s0><s5>07</s5></fC03><fC03 i1="07" i2="X" l="ENG"><s0>Transcription factor</s0><s5>07</s5></fC03><fC03 i1="07" i2="X" l="SPA"><s0>Factor transcripción</s0><s5>07</s5></fC03><fC03 i1="08" i2="X" l="FRE"><s0>Génétique</s0><s5>08</s5></fC03><fC03 i1="08" i2="X" l="ENG"><s0>Genetics</s0><s5>08</s5></fC03><fC03 i1="08" i2="X" l="SPA"><s0>Genética</s0><s5>08</s5></fC03><fC03 i1="09" i2="X" l="FRE"><s0>Hypoparathyroïdie</s0><s5>14</s5></fC03><fC03 i1="09" i2="X" l="ENG"><s0>Hypoparathyroidism</s0><s5>14</s5></fC03><fC03 i1="09" i2="X" l="SPA"><s0>Hipoparatiroidismo</s0><s5>14</s5></fC03><fC03 i1="10" i2="X" l="FRE"><s0>Surdité</s0><s5>15</s5></fC03><fC03 i1="10" i2="X" l="ENG"><s0>Hearing loss</s0><s5>15</s5></fC03><fC03 i1="10" i2="X" l="SPA"><s0>Sordera</s0><s5>15</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Parathyroïde pathologie</s0><s5>19</s5></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Parathyroid diseases</s0><s5>19</s5></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Paratiroides patología</s0><s5>19</s5></fC07><fC07 i1="02" i2="X" l="FRE"><s0>ORL pathologie</s0><s5>20</s5></fC07><fC07 i1="02" i2="X" l="ENG"><s0>ENT disease</s0><s5>20</s5></fC07><fC07 i1="02" i2="X" l="SPA"><s0>ORL patología</s0><s5>20</s5></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Trouble audition</s0><s5>21</s5></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Auditory disorder</s0><s5>21</s5></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Trastorno auditivo</s0><s5>21</s5></fC07><fC07 i1="04" i2="X" l="FRE"><s0>Appareil urinaire pathologie</s0><s5>22</s5></fC07><fC07 i1="04" i2="X" l="ENG"><s0>Urinary system disease</s0><s5>22</s5></fC07><fC07 i1="04" i2="X" l="SPA"><s0>Aparato urinario patología</s0><s5>22</s5></fC07><fC07 i1="05" i2="X" l="FRE"><s0>Maladie congénitale</s0><s5>23</s5></fC07><fC07 i1="05" i2="X" l="ENG"><s0>Congenital disease</s0><s5>23</s5></fC07><fC07 i1="05" i2="X" l="SPA"><s0>Enfermedad congénita</s0><s5>23</s5></fC07><fC07 i1="06" i2="X" l="FRE"><s0>Malformation</s0><s5>24</s5></fC07><fC07 i1="06" i2="X" l="ENG"><s0>Malformation</s0><s5>24</s5></fC07><fC07 i1="06" i2="X" l="SPA"><s0>Malformación</s0><s5>24</s5></fC07><fC07 i1="07" i2="X" l="FRE"><s0>Endocrinopathie</s0><s5>47</s5></fC07><fC07 i1="07" i2="X" l="ENG"><s0>Endocrinopathy</s0><s5>47</s5></fC07><fC07 i1="07" i2="X" l="SPA"><s0>Endocrinopatía</s0><s5>47</s5></fC07><fC07 i1="08" i2="X" l="FRE"><s0>Rein pathologie</s0><s5>48</s5></fC07><fC07 i1="08" i2="X" l="ENG"><s0>Kidney disease</s0><s5>48</s5></fC07><fC07 i1="08" i2="X" l="SPA"><s0>Riñón patología</s0><s5>48</s5></fC07><fN21><s1>122</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard><server><NO>PASCAL 07-0187922 INIST</NO><ET>Functional characterization of GATA3 mutations causing the hypoparathyroidism-deafness-renal (HDR) dysplasia syndrome : Insight into mechanisms of DNA binding by the GATA3 transcription factor</ET><AU>ALI (Asif); CHRISTIE (Paul T.); GRIGORIEVA (Irina V.); HARDING (Brian); VAN ESCH (Hilde); FAISAL AHMED (S.); BITNER-GLINDZICZ (Maria); BLIND (Eberhard); BLOCH (Catherine); CHRISTIN (Patricia); CLAYTON (Peter); GECZ (Jozef); GILBERT-DUSSARDIER (Brigitte); GUILLEN-NAVARRO (Encarna); HACKETT (Anna); HALAC (Isil); HENDY (Geoffrey N.); LALLOO (Fiona); MACHE (Christoph J.); MUGHAL (Zulf); ONG (Albert C. M.); RINAT (Choni); SHAW (Nicholas); SMITHSON (Sarah F.); TOLMIE (John); WEILL (Jacques); NESBIT (M. Andrew); THAKKER (Rajesh V.)</AU><AF>Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, Churchill Hospital/Headington, Oxford OX3 7LJ/Royaume-Uni (1 aut., 2 aut., 3 aut., 4 aut., 27 aut., 28 aut.); Department of Clinical Genetics, Centre for Human Genetics, University Hospital Leuven, Herestraat 49/3000 Leuven/Belgique (5 aut.); Royal Hospital for Sick Children, Dalnair Street/Glasgow G3 8SJ/Royaume-Uni (6 aut.); Clinical and Molecular Genetics Unit, Institute for Child Health/London WC1 N1EH/Royaume-Uni (7 aut.); Department of Medicine, Endocrinology, University of Würtzburg, Josef-Schneider-Str. 2/97080 Würtzburg/Allemagne (8 aut.); Hopital Lenval, 57 Av. De la Californie 06 200/Nice/France (9 aut.); Service de Gènètique Mèdicale, CHU la Milètrie, B.P. 577/86021 Poitiers/France (10 aut., 13 aut.); Royal Manchester Childrens Hospital, Hospital Road, Pendlebury/Manchester M27 4HA/Royaume-Uni (11 aut.); Department of Genetic Medicine, Women's and Children's Hospital, 72 King William Road, North Adelaide/SA 5006, Adelaide/Australie (12 aut.); Unidad de Genetica Medica, Hospital Universitario Virgen de la Arraxaca, Ctra Madrid-Cartagena/El Palmar 30120/Espagne (14 aut.); Hunter Genetics, PO Box 84/Waratah, New South Wales 2298/Australie (15 aut.)</AF><DT>Publication en série; Niveau analytique</DT><SO>Human molecular genetics : (Print); ISSN 0964-6906; Royaume-Uni; Da. 2007; Vol. 16; No. 3; Pp. 265-275; Bibl. 40 ref.</SO><LA>Anglais</LA><EA>The hypoparathyroidism-deafness-renal (HDR) dysplasia syndrome is an autosomal dominant disorder caused by mutations of the dual zinc finger transcription factor, GATA3. We investigated 21 HDR probands and 14 patients with isolated hypoparathyroidism for GATA3 abnormalities. Thirteen different heterozygous germline mutations were identified in patients with HDR. These consisted of three nonsense mutations, six frameshifting deletions, two frameshifting insertions, one missense (Leu348Arg) mutation and one acceptor splice site mutation. The splice site mutation was demonstrated to cause a pre-mRNA processing abnormality leading to the use of an alternative acceptor site 8 bp downstream of the normal site, resulting in a frame-shift and prematurely terminated protein. Electrophoretic mobility shift assays (EMSAs) revealed three classes of GATA3 mutations: those that lead to a loss of DNA binding which represent over 90% of all mutations, and involved a loss of the carboxy-terminal zinc finger; those that resulted in a reduced DNA-binding affinity; and those (e.g. Leu348Arg) that did not alter DNA binding or the affinity but likely altered the conformational change that occurs during binding in the DNA major groove as predicted by a three-dimensional modeling. These results elucidate further the molecular mechanisms underlying the altered functions of mutants of this zinc finger transcription factor and their role in causing this developmental anomaly. No mutations were identified in patients with isolated hypoparathyroidism, thereby indicating that GATA3 abnormalities are more likely to result in two or more of the phenotypic features of the HDR syndrome and not in one, such as isolated hypoparathyroidism.</EA><CC>002A04; 002A07; 002B21D01</CC><FD>Caractérisation; Mutation; Dysplasie rénale; Syndrome; Mécanisme; DNA; Facteur transcription; Génétique; Hypoparathyroïdie; Surdité</FD><FG>Parathyroïde pathologie; ORL pathologie; Trouble audition; Appareil urinaire pathologie; Maladie congénitale; Malformation; Endocrinopathie; Rein pathologie</FG><ED>Characterization; Mutation; Renal dysplasia; Syndrome; Mechanism; DNA; Transcription factor; Genetics; Hypoparathyroidism; Hearing loss</ED><EG>Parathyroid diseases; ENT disease; Auditory disorder; Urinary system disease; Congenital disease; Malformation; Endocrinopathy; Kidney disease</EG><SD>Caracterización; Mutación; Displasia renal; Síndrome; Mecanismo; DNA; Factor transcripción; Genética; Hipoparatiroidismo; Sordera</SD><LO>INIST-22540.354000143293050030</LO><ID>07-0187922</ID></server></inist></record>Pour manipuler ce document sous Unix (Dilib)
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