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

Nadia Falah, Jennifer E. Posey, Willa Thorson, Paul Benke, Mustafa Tekin, Brocha Tarshish, James R. Lupski, Tamar Harel

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1066-1070
Number of pages5
JournalAmerican Journal of Medical Genetics, Part A
Volume173
Issue number4
DOIs
StatePublished - Apr 1 2017

Fingerprint

Waardenburg Syndrome
Peripheral Nervous System Diseases
Disorders of Sex Development
Hirschsprung Disease
Poisons
Demyelinating Diseases
Microarray Analysis
Oligonucleotide Array Sequence Analysis
Phenotype
Mutation
Type 4 Waardenburg syndrome

Keywords

  • 22q duplication syndrome
  • central demyelinating leukodystrophy
  • peripheral demyelinating neuropathy
  • Waardenburg syndrome
  • Waardenburg–Shah syndrome
  • WS4

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

22q11.2q13 duplication including SOX10 causes sex-reversal and peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease. / Falah, Nadia; Posey, Jennifer E.; Thorson, Willa; Benke, Paul; Tekin, Mustafa; Tarshish, Brocha; Lupski, James R.; Harel, Tamar.

In: American Journal of Medical Genetics, Part A, Vol. 173, No. 4, 01.04.2017, p. 1066-1070.

Research output: Contribution to journalArticle

Falah, Nadia ; Posey, Jennifer E. ; Thorson, Willa ; Benke, Paul ; Tekin, Mustafa ; Tarshish, Brocha ; Lupski, James R. ; Harel, Tamar. / 22q11.2q13 duplication including SOX10 causes sex-reversal and peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease. In: American Journal of Medical Genetics, Part A. 2017 ; Vol. 173, No. 4. pp. 1066-1070.
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AU - Thorson, Willa

AU - Benke, Paul

AU - Tekin, Mustafa

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