title: Molecular basis of DFNB73: mutations of BSND can cause nonsyndromic deafness or Bartter syndrome.
abstract: BSND encodes barttin, an accessory subunit of renal and inner ear chloride channels. To date, all mutations of BSND have been shown to cause Bartter syndrome type IV, characterized by significant renal abnormalities and deafness. We identified a BSND mutation (p.I12T) in four kindreds segregating nonsyndromic deafness linked to a 4.04-cM interval on chromosome 1p32.3. The functional consequences of p.I12T differ from BSND mutations that cause renal failure and deafness in Bartter syndrome type IV. p.I12T leaves chloride channel function unaffected and only interferes with chaperone function of barttin in intracellular trafficking. This study provides functional data implicating a hypomorphic allele of BSND as a cause of apparent nonsyndromic deafness. We demonstrate that BSND mutations with different functional consequences are the basis for either syndromic or nonsyndromic deafness.
authors: Section on Human Genetics, Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, NIH, Rockville, MD 20850, USA.
authors: Saima
authors: S
authors: Riazuddin
authors: Saima
authors: S
authors: Anwar
authors: Martin
authors: M
authors: Fischer
authors: Zubair M
authors: ZM
authors: Ahmed
authors: Shahid Y
authors: SY
authors: Khan
authors: Audrey G H
authors: AG
authors: Janssen
authors: Ahmad U
authors: AU
authors: Zafar
authors: Ute
authors: U
authors: Scholl
authors: Tayyab
authors: T
authors: Husnain
authors: Inna A
authors: IA
authors: Belyantseva
authors: Penelope L
authors: PL
authors: Friedman
authors: Sheikh
authors: S
authors: Riazuddin
authors: Thomas B
authors: TB
authors: Friedman
authors: Christoph
authors: C
authors: Fahlke
mesh_terms: D000293:Adolescent; D000328:Adult; D001299:Audiometry; D001477:Bartter Syndrome / Q000235:genetics*; D018118:Chloride Channels / Q000235:genetics*; D019457:Chromosome Breakage; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D004252:DNA Mutational Analysis; D003638:Deafness / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: C440005:BSND protein, human; D018118:Chloride Channels; D005819:Genetic Markers