Evidence of an increased risk of hearing loss in heterozygous carriers in a Wolfram syndrome family

Wolfram syndrome (MIM 222300) is characterized by juvenile-onset diabetes mellitus and optic atrophy. Previous linkage analyses in the United States and UK families have indicated that the gene for Wolfram syndrome (WFS) is localized on the short arm of chromosome 4. We herein confirm the linkage of...

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Published inHuman genetics Vol. 103; no. 4; pp. 470 - 474
Main Authors OHATA, T, KOIZUMI, A, TAKADA, G, KAYO, T, SHOJI, Y, WATANABE, A, MONOH, K, HIGASHI, K, ITO, S, OGAWA, O, WADA, Y
Format Journal Article
LanguageEnglish
Published Heidelberg Springer 01.10.1998
Berlin
New York, NY
Subjects
Adolescent
Adult
Biological and medical sciences
Child
Chromosomes, Human, Pair 4
Complex syndromes
Female
Genetic Markers
Haplotypes
Hearing Loss, Sensorineural - etiology
Heterozygote
Humans
Lod Score
Male
Medical genetics
Medical sciences
Pedigree
Risk
Wolfram Syndrome - genetics
Endocrinopathy
Genetic mapping
Human
Linkage
Auditory disorder
Chromosome B4
Genetic disease
Hearing loss
Eye disease
Association
Wolfram syndrome
Genetics
Complex syndrome
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Summary:Wolfram syndrome (MIM 222300) is characterized by juvenile-onset diabetes mellitus and optic atrophy. Previous linkage analyses in the United States and UK families have indicated that the gene for Wolfram syndrome (WFS) is localized on the short arm of chromosome 4. We herein confirm the linkage of the WFS locus to D4S3023 on 4p with a two-point LOD score of 3.42 in a large Japanese family with Wolfram syndrome. Multipoint linkage analysis revealed the maximum LOD score of 4.82 between D4S3023 and D4S394. We also evaluated putative health risks in carriers by multiple logistic analysis with independent variables, age, gender, and numbers of affected haplotypes and with dependent variables, such as hearing loss, diabetes mellitus, polyuria, incontinence, psychological illness, and visual acuity. The results showed that the putative disease haplotype increased a risk of hearing loss (odds ratio =35.68, 95% confidence interval =4.12-308.95) and diabetes mellitus (odds ratio =7.57, 95% confidence interval =2.03-28.23) independently. This is the first report of an increased health risk of illness in carriers, other than for psychiatric disease.
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ISSN:0340-6717
1432-1203
DOI:10.1007/s004390050852