Evidence for Digenic Inheritance of Nonsyndromic Hereditary Hearing Loss in a Swedish Family

We investigated a Swedish family with nonsyndromic progressive bilateral sensorineural hearing loss. Thirteen candidate loci for autosomal dominant nonsyndromic hearing loss were tested for linkage in this family. We found significant LOD scores (>3) for markers at candidate locus DFNA12 (11q22-q...

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Bibliographic Details
Published in:American journal of human genetics 1998-09, Vol.63 (3), p.786-793
Main Authors: Balciuniene, Jorune, Dahl, Niklas, Borg, Erik, Samuelsson, Eva, Koisti, Markus J., Pettersson, Ulf, Jazin, Elena E.
Format: Article
Language:English
Subjects:
Adult
Audiometry
Biological and medical sciences
Chromosome 1
Chromosome 11
Chromosome Mapping
Chromosomes, Human, Pair 1
Chromosomes, Human, Pair 11
Digenic inheritance
Ear, auditive nerve, cochleovestibular tract, facial nerve: diseases, semeiology
Female
Functional Laterality
Genes, Dominant
Genetic Linkage
Genetic Markers
Haplotypes
Hearing - physiology
Hearing loss
Hearing Loss, Sensorineural - genetics
Hearing Loss, Sensorineural - physiopathology
Humans
Lod Score
Male
Medical sciences
MEDICIN
Medicin och hälsovetenskap
MEDICINE
Non tumoral diseases
Nonsyndromic
Otorhinolaryngology. Stomatology
Pedigree
Recombination, Genetic
Sweden
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Summary:We investigated a Swedish family with nonsyndromic progressive bilateral sensorineural hearing loss. Thirteen candidate loci for autosomal dominant nonsyndromic hearing loss were tested for linkage in this family. We found significant LOD scores (>3) for markers at candidate locus DFNA12 (11q22-q24) and suggestive LOD scores (>2) for markers at locus DFNA2 (1p32). Our results for markers on chromosome 11 narrowed down the candidate region for the DFNA12 locus. A detailed analysis of the phenotypes and haplotypes shared by the affected individuals supported the notion that two genes segregated together with hearing impairment in the family. Severely affected family members had haplotypes linked to the disease allele on both chromosomes 1 and 11, whereas individuals with milder hearing loss had haplotypes linked to the disease allele on either chromosome 1 or chromosome 11. These observations suggest an additive effect of two genes, each gene resulting in a mild and sometimes undiagnosed phenotype, but both together resulting in a more severe phenotype.
ISSN:0002-9297
1537-6605
1537-6605
DOI:10.1086/302012