A novel frameshift mutation in SOX10 causes Waardenburg syndrome with peripheral demyelinating neuropathy, visual impairment and the absence of Hirschsprung disease

Elizabeth A Burke; Kyle E Reichard; Lynne A Wolfe; Brian P Brooks; John J DiGiovanna; Donald W Hadley; Tanya J Lehky; Andrea L Gropman; Cynthia J Tifft; William A Gahl; Camilo Toro; David Adams

doi:10.1002/ajmg.a.61542

A novel frameshift mutation in SOX10 causes Waardenburg syndrome with peripheral demyelinating neuropathy, visual impairment and the absence of Hirschsprung disease

Am J Med Genet A. 2020 May;182(5):1278-1283. doi: 10.1002/ajmg.a.61542. Epub 2020 Mar 9.

Authors

Elizabeth A Burke¹, Kyle E Reichard¹, Lynne A Wolfe^{1

2}, Brian P Brooks³, John J DiGiovanna⁴, Donald W Hadley^{2

5}, Tanya J Lehky⁶, Andrea L Gropman^{5

7}, Cynthia J Tifft^{1

2}, William A Gahl^{1

2

8}, Camilo Toro^{1

2}, David Adams^{1

2}

Affiliations

¹ NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
² Office of the Clinical Director, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
³ Ophthalmic Genetics and Visual Function Branch, National Eye Institute, NIH, Bethesda, Maryland, USA.
⁴ Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA.
⁵ Human Development Section, Medical Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
⁶ Electromyography Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland, USA.
⁷ Department of Neurology, Children's National Medical Center, Washington, District of Columbia, USA.
⁸ Section on Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.

Abstract

Waardenburg syndrome (WS) is a group of genetic disorders associated with varying components of sensorineural hearing loss and abnormal pigmentation of the hair, skin, and eyes. There exist four different WS subtypes, each defined by the absence or presence of additional features. One of the genes associated with WS is SOX10, a key transcription factor for the development of neural crest-derived lineages. Here we report a 12-year-old boy with a novel de novo SOX10 frameshift mutation and unique combination of clinical features including primary peripheral demyelinating neuropathy, hearing loss and visual impairment but absence of Hirschsprung disease and the typical pigmentary changes of hair or skin. This expands the spectrum of currently recognized phenotypes associated with WS and illustrates the phenotypic heterogeneity of SOX10-associated WS.

Keywords: Cochlear implant; SOX10; Waardenburg syndrome.

Publication types

Case Reports
Research Support, N.I.H., Intramural

MeSH terms

Autoimmune Diseases of the Nervous System / genetics
Autoimmune Diseases of the Nervous System / physiopathology
Child
Demyelinating Diseases / genetics
Demyelinating Diseases / physiopathology
Frameshift Mutation / genetics
Genetic Predisposition to Disease*
Hirschsprung Disease / genetics*
Hirschsprung Disease / physiopathology
Humans
Male
Pedigree
Phenotype
SOXE Transcription Factors / genetics*
Waardenburg Syndrome / genetics*
Waardenburg Syndrome / physiopathology

Substances

SOX10 protein, human
SOXE Transcription Factors

Grants and funding

Z99 HG999999/ImNIH/Intramural NIH HHS/United States