Autosomal dominant optic neuropathy and sensorineual hearing loss associated with a novel mutation of WFS1

• Published in: Molecular vision Vol. 16; pp. 26 - 35
• Main Authors: Hogewind, Barend F T, Pennings, Ronald J E, Hol, Frans A, Kunst, Henricus P M, Hoefsloot, Elisabeth H, Cruysberg, Johannes R M, Cremers, Cor W R J
• Format: Journal Article
• Language: English
• Published: United States Molecular Vision 12.01.2010
• Subjects: Adult; Aged, 80 and over; Amino Acid Sequence; Base Sequence; Color vision; Conserved Sequence; Deafness; Diabetes Mellitus - genetics; DNA Mutational Analysis; Evolution, Molecular; Exons; Family; Fasting; Female; Genes, Dominant - genetics; Genetic Association Studies; Genetic Predisposition to Disease; Glucose; Glucose tolerance; Hearing loss; Hearing Loss, Sensorineural - complications; Hearing Loss, Sensorineural - genetics; Hearing Loss, Sensorineural - physiopathology; Hearing Tests; Humans; Male; Membrane Proteins - chemistry; Membrane Proteins - genetics; Middle Aged; Missense mutation; Mitochondria; Molecular Sequence Data; Mutation - genetics; Ocular Physiological Phenomena; Optic nerve; Optic Nerve Diseases - complications; Optic Nerve Diseases - genetics; Optic Nerve Diseases - physiopathology; Optic neuropathy; Optics; Pedigree; Phenotype; Vision; Young Adult
• ISSN: 1090-0535; 1090-0535

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. 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. 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. This study describes the phenotype of a family with autosomal dominant optic neuropathy and hearing impairment associated with a novel missense mutation in WFS1.