Non-syndromic progressive hearing loss DFNA38 is caused by heterozygous missense mutation in the Wolfram syndrome gene WFS1

A) was shared by all deaf members of the family and was specific to deaf individuals. The causal relationship between this missense mutation and deafness was supported by two observations based on haplotype and mutation analysis of the kindred. First, a relative homozygous for the mutation was diagnosed at age 3 years with insulin-dependent diabetes mellitus, the central feature of Wolfram syndrome. Second, two relatives with normal hearing had an identical haplotype to that defining DFNA38, with the exception of the base pair at position 2146. Other rare variants of WFS1 co-inherited with deafness in the family could be excluded as disease-causing mutations on the basis of this hearing-associated haplotype. The possibility that 'mild' mutations in WFS1 might be a cause of non-syndromic deafness in the general population should be explored. -->
ISSN: 0964-6906
Přístupová URL adresa: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d86bddea3f5375a20f6c2ad6c49e951b
https://pubmed.ncbi.nlm.nih.gov/11709538
Rights: OPEN
Přírůstkové číslo: edsair.doi.dedup.....d86bddea3f5375a20f6c2ad6c49e951b
Autor: T L, Young, E, Ives, E, Lynch, R, Person, S, Snook, L, MacLaren, T, Cater, A, Griffin, B, Fernandez, M K, Lee, M C, King, T, Cator
Rok vydání: 2001
Předmět:
Male
endocrine system diseases
DNA Mutational Analysis
Deafness
Loss of heterozygosity
Mice
Missense mutation
Cloning
Molecular
Genetics (clinical)
Genetics
education.field_of_study
Homozygote
Chromosome Mapping
General Medicine
Pedigree
Phenotype
Mutation (genetic algorithm)
Disease Progression
Female
medicine.symptom
Chromosomes
Human
Pair 4
Heterozygote
Wolfram syndrome
Hearing loss
Hearing Loss
Sensorineural
Population
Molecular Sequence Data
Mutation
Missense
Biology
Synteny
Atrophy
otorhinolaryngologic diseases
medicine
Animals
Humans
Amino Acid Sequence
education
Molecular Biology
Family Health
Base Sequence
Sequence Homology
Amino Acid
Haplotype
nutritional and metabolic diseases
Membrane Proteins
Wolfram Syndrome
DNA
medicine.disease
Mice
Inbred C57BL
Haplotypes
Sequence Alignment
Microsatellite Repeats
Zdroj: Scopus-Elsevier
ISSN: 0964-6906
Popis: Dominantly inherited progressive hearing loss DFNA38 is caused by heterozygosity for a novel mutation in WFS1, the gene for recessively inherited Wolfram syndrome. Wolfram syndrome is defined by juvenile diabetes mellitus and optic atrophy and may include progressive hearing loss and other neurological symptoms. Heterozygotes for other Wolfram syndrome mutations generally have normal hearing. Dominant deafness defined by DFNA38 is more severe than deafness of Wolfram syndrome patients and lacks any syndromic features. In a six-generation kindred from Newfoundland, Canada, WFS1 Ala716Thr (2146 G-->A) was shared by all deaf members of the family and was specific to deaf individuals. The causal relationship between this missense mutation and deafness was supported by two observations based on haplotype and mutation analysis of the kindred. First, a relative homozygous for the mutation was diagnosed at age 3 years with insulin-dependent diabetes mellitus, the central feature of Wolfram syndrome. Second, two relatives with normal hearing had an identical haplotype to that defining DFNA38, with the exception of the base pair at position 2146. Other rare variants of WFS1 co-inherited with deafness in the family could be excluded as disease-causing mutations on the basis of this hearing-associated haplotype. The possibility that 'mild' mutations in WFS1 might be a cause of non-syndromic deafness in the general population should be explored.
Databáze: OpenAIRE
Externí odkaz: