The authors declare no conflict of interest.
Phenotypic similarities and differences in patients with a p.Met112Ile mutation in SOX10
Article first published online: 20 MAY 2014
© 2014 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 164, Issue 9, pages 2344–2350, September 2014
How to Cite
2014. Phenotypic similarities and differences in patients with a p.Met112Ile mutation in SOX10. Am J Med Genet Part A 164A:2344–2350., , , , , , , , .
- Issue published online: 13 AUG 2014
- Article first published online: 20 MAY 2014
- Manuscript Accepted: 18 APR 2014
- Manuscript Received: 9 DEC 2013
- Institut de la Santé et de la Recherche Médicale (INSERM)
- Assistance Publique des Hôpitaux de Paris (AP-HP)
- Agence Nationale de la Recherche (ANR-JCJC-2010)
- Fondation pour la Recherche Médicale (FRM)
- SOX10 protein;
- Waardenburg syndrome;
- Hirschsprung disease;
- pigmentation disorders;
- proto-oncogene protein;
Waardenburg syndrome (WS) is characterized by an association of pigmentation abnormalities and sensorineural hearing loss. Four types, defined on clinical grounds, have been delineated, but this phenotypic classification correlates imperfectly with known molecular anomalies. SOX10 mutations have been found in patients with type II and type IV WS (i.e., with Hirschsprung disease), more complex syndromes, and partial forms of the disease. The phenotype induced by SOX10 mutations is highly variable and, except for the neurological forms of the disease, no genotype–phenotype correlation has been characterized to date. There is no mutation hotspot in SOX10 and most cases are sporadic, making it particularly difficult to correlate the phenotypic and genetic variability. This study reports on three independent families with SOX10 mutations predicted to result in the same missense mutation at the protein level (p.Met112Ile), offering a rare opportunity to improve our understanding of the mechanisms underlying phenotypic variability. The pigmentation defects of these patients are very similar, and the neurological symptoms showed a somewhat similar evolution over time, indicating a potential partial genotype–phenotype correlation. However, variability in gastrointestinal symptoms suggests that other genetic factors contribute to the expression of these phenotypes. No correlation between the rs2435357 polymorphism of RET and the expression of Hirschsprung disease was found. In addition, one of the patients has esophageal achalasia, which has rarely been described in WS. © 2014 Wiley Periodicals, Inc.