Novel missense WFS1 variant causing autosomal dominant atypical Wolfram syndrome

Ophthalmic Genet. 2022 Aug;43(4):567-572. doi: 10.1080/13816810.2022.2068038. Epub 2022 Apr 21.


Background: In contrast to the classic autosomal recessive Wolfram syndrome, Wolfram-like syndrome (WLS) is an autosomal dominant disease caused by heterozygous variants in the WFS1 gene. Here, we present deep phenotyping of a mother and son with a WFS1 variant NM_006005.3:c.2508 G > T, p. (Lys836Asn) detected with next-generation sequencing, which is novel at the nucleotide level. In this Greek family, the proband and mother had sensorineural hearing loss and mild non-progressive vision loss with optic nerve atrophy. An initial optic atrophy panel that did not test for WFS1 was unremarkable, but a broader inherited retinal dystrophy panel found the WFS1 variant.

Conclusion: This study highlights the importance of including WFS1 sequencing in the evaluation of optic nerve atrophy to discover syndromic conditions.

Keywords: WFS1; Wolfram-like syndrome; Wolframin; atypical Wolfram-like syndrome; optic atrophy; sensorineural hearing loss.

MeSH terms

  • Atrophy
  • Hearing Loss, Sensorineural* / diagnosis
  • Hearing Loss, Sensorineural* / genetics
  • Humans
  • Membrane Proteins / genetics
  • Mutation
  • Mutation, Missense
  • Optic Atrophy* / diagnosis
  • Optic Atrophy* / genetics
  • Wolfram Syndrome* / diagnosis
  • Wolfram Syndrome* / genetics


  • Membrane Proteins