title: Nonsense mutation of the stereociliar membrane protein gene PTPRQ in human hearing loss DFNB84.
abstract: BACKGROUND
  Moderate to severe prelingual hearing impairment (DFNB84) was observed in an extended consanguineous Palestinian kindred. All affected relatives shared a 12.5 MB homozygous haplotype on chromosome 12q21 with lod score 4.30. This homozygous region harbours the protein tyrosine phosphatase receptor Q gene PTPRQ, which is known to be essential to hearing in mouse.
  
  
  METHODS
  Candidate genes in the 12.5 MB homozygous region were characterized genomically and sequenced in deaf and hearing relatives in the family.
  
  
  RESULTS
  Sequence of PTPRQ in affected individuals in the extended kindred revealed c.1285C-->T, leading to p.Gln429Stop. This nonsense mutation co-segregated with hearing loss in the family and was homozygous in all affected relatives. The mutation did not appear among 288 Palestinian controls (576 chromosomes), all adults with normal hearing. No homozygous mutations in PTPRQ appeared in any of 218 other probands with hearing loss.
  
  
  CONCLUSIONS
  Identification of the DFNB84 gene represents the first identification of PTPRQ mutation in human hearing loss.
authors.affiliation: Department of Life Sciences, Bethlehem University, Bethlehem, Palestinian National Authority.
authors.forename: Hashem
authors.initials: H
authors.lastname: Shahin
authors.forename: Michael
authors.initials: M
authors.lastname: Rahil
authors.forename: Amal
authors.initials: A
authors.lastname: Abu Rayan
authors.forename: Karen B
authors.initials: KB
authors.lastname: Avraham
authors.forename: Mary-Claire
authors.initials: MC
authors.lastname: King
authors.forename: Moien
authors.initials: M
authors.lastname: Kanaan
authors.forename: Tom
authors.initials: T
authors.lastname: Walsh
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002923:Cilia / Q000235:genetics*; D018389:Codon, Nonsense / Q000235:genetics*; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D034381:Hearing Loss / Q000201:enzymology* / Q000235:genetics*; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D010375:Pedigree; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D008565:Membrane Proteins; C516917:PTPRQ protein, human; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3