Autoimmune disease in a DFNA6/14/38 family carrying a novel missense mutation in WFS1

Michael S. Hildebrand, Jessica L. Sorensen, Maren Jensen, William J. Kimberling, Richard J.H. Smith

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Most familial cases of autosomal dominant low frequency sensorineural hearing loss (LFSNHL) are attributable to mutations in the wolframin syndrome 1 (WFS1) gene at the DFNA6/14/38 locus. WFS1 mutations at this locus were first described in 2001 in six families segregating LFSNHL that was non-progressive below 2,000 Hz; the causative mutations all clustered in the C-terminal domain of the wolframin protein. Mutations in WFS1 also cause Wolfram syndrome (WS), an autosomal recessive neurodegenerative disorder defined by diabetes mellitus, optic atrophy and often deafness, while numerous single nucleotide polymorphisms (SNPs) in WFS1 have been associated with increased risk for diabetes mellitus, psychiatric illnesses and Parkinson disease. This study was conducted in an American family segregating autosomal dominant LFSNHL. Two hearing impaired family members also had autoimmune diseases - Graves disease (GD) and Crohn disease (CD). Based on the low frequency audioprofile, mutation screening of WFS1 was completed and a novel missense mutation (c.2576G → A) that results in an arginine-to-glutamine substitution (p.R859Q) was identified in the C-terminal domain of the wolframin protein where most LFSNHL-causing mutations cluster. The family member with GD also carried polymorphisms in WFS1 that have been associated with other autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)2258-2265
Number of pages8
JournalAmerican Journal of Medical Genetics, Part A
Issue number17
StatePublished - Sep 1 2008
Externally publishedYes


  • Crohn disease
  • DFNA6/14/38
  • Graves disease
  • Missense mutation
  • WFS1

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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