De novo microdeletions and point mutations affecting SOX2 in three individuals with intellectual disability but without major eye malformations.

Autor: Dennert N; Institute of Human Genetics, University of Bonn, Bonn, Germany., Engels H; Institute of Human Genetics, University of Bonn, Bonn, Germany., Cremer K; Institute of Human Genetics, University of Bonn, Bonn, Germany., Becker J; Institute of Human Genetics, University of Bonn, Bonn, Germany., Wohlleber E; Institute of Human Genetics, University of Bonn, Bonn, Germany., Albrecht B; Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany., Ehret JK; Institute of Human Genetics, University of Bonn, Bonn, Germany., Lüdecke HJ; Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany.; Institute of Human Genetics, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany., Suri M; Nottingham Clinical Genetics Service, Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, United Kingdom., Carignani G; Medical Genetics Unit, University of Siena, Siena, Italy., Renieri A; Medical Genetics Unit, University of Siena, Siena, Italy., Kukuk GM; Department of Radiology, University of Bonn, Bonn, Germany., Wieland T; Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany., Andrieux J; Laboratory of Medical Genetics, Hôpital Jeanne de Flandre University Hospital, Lille, France., Strom TM; Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany., Wieczorek D; Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany.; Institute of Human Genetics, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany., Dieux-Coëslier A; Clinical Genetics, Hôpital Jeanne de France University Hospital, Lille, France., Zink AM; Institute of Human Genetics, University of Bonn, Bonn, Germany.
Jazyk: angličtina
Zdroj: American journal of medical genetics. Part A [Am J Med Genet A] 2017 Feb; Vol. 173 (2), pp. 435-443. Date of Electronic Publication: 2016 Nov 14.
DOI: 10.1002/ajmg.a.38034
Abstrakt: Loss-of-function mutations and deletions of the SOX2 gene are known to cause uni- and bilateral anophthalmia and microphthalmia as well as related disorders such as anophthalmia-esophageal-genital syndrome. Thus, anophthalmia/microphthalmia is the primary indication for targeted, "phenotype first" analyses of SOX2. However, SOX2 mutations are also associated with a wide range of non-ocular abnormalities, such as postnatal growth retardation, structural brain anomalies, hypogenitalism, and developmental delay. The present report describes three patients without anophthalmia/microphthalmia and loss-of-function mutations or microdeletions of SOX2 who had been investigated in a "genotype first" manner due to intellectual disability/developmental delay using whole exome sequencing or chromosomal microarray analyses. This result prompted us to perform SOX2 Sanger sequencing in 192 developmental delay/intellectual disability patients without anophthalmia or microphthalmia. No additional SOX2 loss-of-function mutations were detected in this cohort, showing that SOX2 is clearly not a major cause of intellectual disability without anophthalmia/microphthalmia. In our three patients and four further, reported "genotype first" SOX2 microdeletion patients, anophthalmia/microphthalmia was present in less than half of the patients. Thus, SOX2 is another example of a gene whose clinical spectrum is broadened by the generation of "genotype first" findings using hypothesis-free, genome-wide methods. © 2016 Wiley Periodicals, Inc.
(© 2016 Wiley Periodicals, Inc.)
Databáze: MEDLINE
Externí odkaz: