[Heterogeneous mutations of Wolfram syndrome I gene responsible for low frequency nonsyndromic hearing loss].
OBJECTIVE
To explore the mutations of Wolfram syndrome I gene (WFS1) in families affected by non-syndromic low frequency sensorineural hearing loss (NS-LFSNHL).


METHODS
Twenty eight individuals from 6 pedigrees with hereditary non-syndromic low frequency sensorineural hearing loss as a dominant trait and cases of control were collected in the present study. The coding sequence of WFS1 gene was amplified by polymerase chain reaction (PCR), and direct DNA sequencing was performed to screen the entire coding region of the WFS1 gene for mutations in the WFS1.


RESULTS
Three heterozygous missense mutations (2016 G-->T, 2379 G-->4A, 2766 G-->A) in the WFS1 gene were found in two families. Mutations in WFS1 were identified in all patients tested of the two pedigrees. None of the mutations was found in at least 280 control chromosomes and normal individuals of the families. These missense mutations affecting conserved amino acids in two pedigrees.


CONCLUSIONS
Mutations in WFS1 are one of causes of non-syndromic low frequency sensorineural hearing loss, and the majority of mutations are missense mutations. Genetic counseling and genetic testing may be useful in the management of patients with this type of hearing loss.
Liu
Yu-he
YH
Department of Otorhinolaryngology Head and Neck Surgery, First Hospital of Peking University, Beijing 100034, China. liuyuhe@xinhuanet.com
Ke
Xiao-mei
XM
Xiao
Shui-fang
SF
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D034381:Hearing Loss / Q000209:etiology / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D014929:Wolfram Syndrome / Q000235:genetics*; D055815:Young Adult
D008565:Membrane Proteins; C114987:wolframin protein