Mutations in STRA6 Cause a Broad Spectrum of Malformations Including Anophthalmia, Congenital Heart Defects, Diaphragmatic Hernia, Alveolar Capillary Dysplasia, Lung Hypoplasia, and Mental Retardation
| العنوان: | Mutations in STRA6 Cause a Broad Spectrum of Malformations Including Anophthalmia, Congenital Heart Defects, Diaphragmatic Hernia, Alveolar Capillary Dysplasia, Lung Hypoplasia, and Mental Retardation |
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| المؤلفون: | Gunnar Houge, Axel von der Wense, Christian Becker, Pierre Bitoun, Francesca Pasutto, Gudrun Nürnberg, David Chitayat, John Tolmie, Peter Meinecke, David R. FitzPatrick, André Reis, Anne Slavotinek, Geert Mortier, Gerhard Hammersen, Sarah Keating, Raoul C.M. Hennekam, Heinrich Sticht, Peter Nürnberg, Heidemarie Schirmer-Zimmermann, Lorena Fernández-Martínez, Gabriele Gillessen-Kaesbach, Frank Brasch, Anita Rauch |
| المساهمون: | ANS - Amsterdam Neuroscience, APH - Amsterdam Public Health, Paediatric Genetics |
| المصدر: | American journal of human genetics, 80(3), 550-560. Cell Press Pasutto, F, Sticht, H, Hammersen, G, Gillessen-Kaesbach, G, Fitzpatrick, D R, Nürnberg, G, Brasch, F, Schirmer-Zimmermann, H, Tolmie, J L, Chitayat, D, Houge, G, Fernández-Martínez, L, Keating, S, Mortier, G, Hennekam, R C M, von der Wense, A, Slavotinek, A, Meinecke, P, Bitoun, P, Becker, C, Nürnberg, P, Reis, A & Rauch, A 2007, ' Mutations in STRA6 cause a broad spectrum of malformations including anophthalmia, congenital heart defects, diaphragmatic hernia, alveolar capillary dysplasia, lung hypoplasia, and mental retardation ', American Journal of Human Genetics, vol. 80, no. 3, pp. 550-60 . https://doi.org/10.1086/512203Test |
| بيانات النشر: | Elsevier BV, 2007. |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | Receptors, Cell Surface/genetics, Male, Alveolar capillary dysplasia, Hernia, Diaphragmatic/genetics, Vitamin A transport, Consanguinity, Abnormalities, Multiple/genetics, Missense mutation, Genetics(clinical), Diaphragmatic hernia, Phosphorylation, Lung/abnormalities, Lung, Genetics (clinical), Genetics, Pulmonary Alveoli/blood supply, Disease gene identification, Heart Defects, Congenital/genetics, Pedigree, Transmembrane domain, Female, Adult, Heart Defects, Congenital, Mutation/genetics, Adolescent, Lung/pathology, Molecular Sequence Data, Receptors, Cell Surface, Biology, Chromosome 15, Report, Intellectual Disability, medicine, Humans, Abnormalities, Multiple, Amino Acid Sequence, Membrane Proteins/genetics, Hernia, Diaphragmatic, Anophthalmia, Anophthalmos/genetics, Sequence Homology, Amino Acid, Infant, Newborn, Anophthalmos, Infant, Membrane Proteins, medicine.disease, Intellectual Disability/genetics, Capillaries, Pulmonary Alveoli, Mutation, Capillaries/abnormalities, Membrane Proteins/metabolism |
| الوصف: | We observed two unrelated consanguineous families with malformation syndromes sharing anophthalmia and distinct eyebrows as common signs, but differing for alveolar capillary dysplasia or complex congenital heart defect in one and diaphragmatic hernia in the other family. Homozygosity mapping revealed linkage to a common locus on chromosome 15, and pathogenic homozygous mutations were identified in STRA6, a member of a large group of "stimulated by retinoic acid" genes encoding novel transmembrane proteins, transcription factors, and secreted signaling molecules or proteins of largely unknown function. Subsequently, homozygous STRA6 mutations were also demonstrated in 3 of 13 patients chosen on the basis of significant phenotypic overlap to the original cases. While a homozygous deletion generating a premature stop codon (p.G50AfsX22) led to absence of the immunoreactive protein in patient's fibroblast culture, structural analysis of three missense mutations (P90L, P293L, and T321P) suggested significant effects on the geometry of the loops connecting the transmembrane helices of STRA6. Two further variations in the C-terminus (T644M and R655C) alter specific functional sites, an SH2-binding motif and a phosphorylation site, respectively. STRA6 mutations thus define a pleiotropic malformation syndrome representing the first human phenotype associated with mutations in a gene from the "STRA" group. |
| وصف الملف: | application/pdf |
| تدمد: | 0002-9297 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f10b189ca45bb1063918f5ed1932b6bfTest https://doi.org/10.1086/512203Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f10b189ca45bb1063918f5ed1932b6bf |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00029297 |
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