22q11.2q13 duplication including SOX10 causes sex-reversal and peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease.

Title22q11.2q13 duplication including SOX10 causes sex-reversal and peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease.
Publication TypeJournal Article
Year of Publication2017
AuthorsFalah, N, Posey, JE, Thorson, W, Benke, P, Tekin, M, Tarshish, B, Lupski, JR, Harel, T
JournalAm J Med Genet A
Volume173
Issue4
Pagination1066-1070
Date Published2017 Apr
ISSN1552-4833
Abstract

Diagnosis of genetic syndromes may be difficult when specific components of a disorder manifest at a later age. We present a follow up of a previous report [Seeherunvong et al., (2004); AJMGA 127: 149-151], of an individual with 22q duplication and sex-reversal syndrome. The subject's phenotype evolved to include peripheral and central demyelination, Waardenburg syndrome type IV, and Hirschsprung disease (PCWH; MIM 609136). DNA microarray analysis defined the duplication at 22q11.2q13, including SOX10. Sequencing of the coding region of SOX10 did not reveal any mutations. Our data suggest that SOX10 duplication can cause disorders of sex development and PCWH, supporting the hypothesis that SOX10 toxic gain of function rather than dominant negative activity underlies PCWH.

DOI10.1002/ajmg.a.38109
Alternate JournalAm. J. Med. Genet. A
PubMed ID28328136
Grant ListUM1 HG006542 / HG / NHGRI NIH HHS / United States