Autosomal dominant optic neuropathy and sensorineual hearing loss associated with a novel mutation of WFS1.
OBJECTIVE
To describe the phenotype of a novel Wolframin (WFS1) mutation in a family with autosomal dominant optic neuropathy and deafness. The study is designed as a retrospective observational case series.


METHODS
Seven members of a Dutch family underwent ophthalmological, otological, and genetical examinations in one institution. Fasting serum glucose was assessed in the affected family members.


RESULTS
All affected individuals showed loss of neuroretinal rim of the optic nerve at fundoscopy with enlarged blind spots at perimetry. They showed a red-green color vision defect at color vision tests and deviations at visually evoked response tests. The audiograms of the affected individuals showed hearing loss and were relatively flat. The unaffected individuals showed no visual deviations or hearing impairment. The affected family members had no glucose intolerance. Leber hereditary optic neuropathy (LHON) mitochondrial mutations and mutations in the Optic atrophy-1 gene (OPA1) were excluded. In the affected individuals, a novel missense mutation c.2508G>C (p.Lys836Asn) in exon 8 of WFS1 was identified.


CONCLUSIONS
This study describes the phenotype of a family with autosomal dominant optic neuropathy and hearing impairment associated with a novel missense mutation in WFS1.
Hogewind
Barend F T
BF
Department of Ophthalmology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. fhogewind@hotmail.com
Pennings
Ronald J E
RJ
Hol
Frans A
FA
Kunst
Henricus P M
HP
Hoefsloot
Elisabeth H
EH
Cruysberg
Johannes R M
JR
Cremers
Cor W R J
CW
D000328:Adult; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001483:Base Sequence; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D003920:Diabetes Mellitus / Q000235:genetics; D019143:Evolution, Molecular; D005190:Family; D005260:Female; D005799:Genes, Dominant / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006319:Hearing Loss, Sensorineural / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D006320:Hearing Tests; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009799:Ocular Physiological Phenomena; D009901:Optic Nerve Diseases / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D010641:Phenotype; D055815:Young Adult
D008565:Membrane Proteins; C114987:wolframin protein