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De novo microdeletions and point mutations affecting SOX2 in three individuals with intellectual disability but without major eye malformations.
- Source :
- American Journal of Medical Genetics. Part A; Feb2017, Vol. 173 Issue 2, p435-443, 9p
- Publication Year :
- 2017
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15524825
- Volume :
- 173
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- American Journal of Medical Genetics. Part A
- Publication Type :
- Academic Journal
- Accession number :
- 120810609
- Full Text :
- https://doi.org/10.1002/ajmg.a.38034