Nonsense mutation of the stereociliar membrane protein gene PTPRQ in human hearing loss DFNB84.
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.
Shahin
Hashem
H
Department of Life Sciences, Bethlehem University, Bethlehem, Palestinian National Authority.
Rahil
Michael
M
Abu Rayan
Amal
A
Avraham
Karen B
KB
King
Mary-Claire
MC
Kanaan
Moien
M
Walsh
Tom
T
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*
D018389:Codon, Nonsense; D008565:Membrane Proteins; C516917:PTPRQ protein, human; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3