Prestin, a cochlear motor protein, is defective in non-syndromic hearing loss.
Prestin, a membrane protein that is highly and almost exclusively expressed in the outer hair cells (OHCs) of the cochlea, is a motor protein which senses membrane potential and drives rapid length changes in OHCs. Surprisingly, prestin is a member of a gene family, solute carrier (SLC) family 26, that encodes anion transporters and related proteins. Of nine known human genes in this family, three (SLC26A2, SLC26A3 and SLC26A4) are associated with different human hereditary diseases. The restricted expression of prestin in OHCs, and its proposed function as a mechanical amplifier, make it a strong candidate gene for human deafness. Here we report the cloning and characterization of four splicing isoforms for the human prestin gene (SLC26A5a, b, c and d). SLC26A5a is the predominant form of prestin whereas the others showed limited distribution associated with certain developmental stages. Based on the functional importance of prestin we screened for possible mutations involving the prestin gene in a group of deaf probands. We have identified a 5'-UTR splice acceptor mutation (IVS2-2A>G) in exon 3 of the prestin gene, which is responsible for recessive non-syndromic deafness in two unrelated families. In addition, a high frequency of heterozygosity for the same mutation was observed in these subjects, suggesting the possibility of semi-dominant influence of the mutation in causing hearing loss. Finally, the observation of this mutation only in the Caucasian probands indicated an association with a specific ethnic background. This study thereby reveals an essential function of prestin in human auditory processing.
Liu
Xue Zhong
XZ
Department of Otolaryngology, University of Miami, Miami, FL 33101, USA. xliu@med.miami.edu
Ouyang
Xiao Mei
XM
Xia
Xia Juan
XJ
Zheng
Jing
J
Pandya
Arti
A
Li
Fang
F
Du
Li Lin
LL
Welch
Katherine O
KO
Petit
Christine
C
Smith
Richard J H
RJ
Webb
Bradley T
BT
Yan
Denise
D
Arnos
Kathleen S
KS
Corey
David
D
Dallos
Peter
P
Nance
Walter E
WE
Chen
Zheng Yi
ZY
D017398:Alternative Splicing; D027321:Anion Transport Proteins; D005260:Female; D034381:Hearing Loss / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D020033:Protein Isoforms; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D020539:Sequence Analysis, Protein; D000076988:Sulfate Transporters
D027321:Anion Transport Proteins; D020033:Protein Isoforms; D011506:Proteins; C498719:SLC26A5 protein, human; D000076988:Sulfate Transporters