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Am J Hum Genet. 2006 Jan;78(1):144-52. Epub 2005 Nov 21.

Mutations in a novel isoform of TRIOBP that encodes a filamentous-actin binding protein are responsible for DFNB28 recessive nonsyndromic hearing loss.

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1
Department of Life Sciences, Bethlehem University, Bethlehem.

Abstract

In a large consanguineous Palestinian kindred, we previously mapped DFNB28--a locus associated with recessively inherited, prelingual, profound sensorineural hearing impairment--to chromosome 22q13.1. We report here that mutations in a novel 218-kDa isoform of TRIOBP (TRIO and filamentous actin [F-actin] binding protein) are associated with DFNB28 hearing loss in a total of nine Palestinian families. Two nonsense mutations (R347X and Q581X) truncate the protein, and a potentially deleterious missense mutation (G1019R) occurs in a conserved motif in a putative SH3-binding domain. In seven families, 27 deaf individuals are homozygous for one of the nonsense mutations; in two other families, 3 deaf individuals are compound heterozygous for the two nonsense mutations or for Q581X and G1019R. The novel long isoform of TRIOBP has a restricted expression profile, including cochlea, retina, and fetal brain, whereas the original short isoform is widely expressed. Antibodies to TRIOBP reveal expression in sensory cells of the inner ear and colocalization with F-actin along the length of the stereocilia.

PMID:
16385458
PMCID:
PMC1380212
DOI:
10.1086/499495
[Indexed for MEDLINE]
Free PMC Article
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