Phenotypic similarities and differences in patients with a p.Met112Ile mutation in SOX10. Issue 9 (20th May 2014)

• Record Type: Journal Article
• Authors: Pingault, Veronique; Pierre‐Louis, Laurence; Chaoui, Asma; Verloes, Alain; Sarrazin, Elisabeth; Brandberg, Goran; Bondurand, Nadege; Uldall, Peter; Manouvrier‐Hanu, Sylvie
• Is Part Of: American journal of medical genetics. Volume 164:Issue 9(2014.)
• Page Start: 2344
• Page End: 2350
• Publication Date: 2014-05-20
• Subjects: Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.36612
• Languages: English
• ISSNs: 1552-4825

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ajmga36612-sec-0001" sec-type="section"> <p>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. <italic>SOX10</italic> 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 <italic>SOX10</italic> 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 <italic>SOX10</italic> and most cases are sporadic, making it particularly difficult to correlate the phenotypic and genetic variability. This study reports on three independent families with <italic>SOX10</italic> 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 <italic>RET</italic> 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.</p> </sec> </abstract>