title: Molecular and clinical studies of X-linked deafness among Pakistani families.
abstract: There are 68 sex-linked syndromes that include hearing loss as one feature and five sex-linked nonsyndromic deafness loci listed in the OMIM database. The possibility of additional such sex-linked loci was explored by ascertaining three unrelated Pakistani families (PKDF536, PKDF1132 and PKDF740) segregating X-linked recessive deafness. Sequence analysis of POU3F4 (DFN3) in affected members of families PKDF536 and PKDF1132 revealed two novel nonsense mutations, p.Q136X and p.W114X, respectively. Family PKDF740 is segregating congenital blindness, mild-to-profound progressive hearing loss that is characteristic of Norrie disease (MIM#310600). Sequence analysis of NDP among affected members of this family revealed a novel single nucleotide deletion c.49delG causing a frameshift and premature truncation (p.V17fsX1) of the encoded protein. These mutations were not found in 150 normal DNA samples. Identification of pathogenic alleles causing X-linked recessive deafness will improve molecular diagnosis, genetic counseling and molecular epidemiology of hearing loss among Pakistanis.
authors.affiliation: National Center of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
authors.forename: Ali M
authors.initials: AM
authors.lastname: Waryah
authors.forename: Zubair M
authors.initials: ZM
authors.lastname: Ahmed
authors.forename: Munir A
authors.initials: MA
authors.lastname: Bhinder
authors.forename: Munir A
authors.initials: MA
authors.lastname: Binder
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Choo
authors.forename: Robert A
authors.initials: RA
authors.lastname: Sisk
authors.forename: Mohsin
authors.initials: M
authors.lastname: Shahzad
authors.forename: Shaheen N
authors.initials: SN
authors.lastname: Khan
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Friedman
authors.forename: Sheikh
authors.initials: S
authors.lastname: Riazuddin
authors.forename: Saima
authors.initials: S
authors.lastname: Riazuddin
mesh_terms: D001483:Base Sequence; D001766:Blindness / Q000151:congenital / Q000235:genetics; D003638:Deafness / Q000235:genetics*; D005190:Family; D050172:Genes, X-Linked; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009422:Nervous System Diseases / Q000235:genetics; D050809:POU Domain Factors / Q000235:genetics; D010154:Pakistan; D010375:Pedigree; D012162:Retinal Degeneration; D013036:Spasms, Infantile / Q000235:genetics
chemical_list: D050809:POU Domain Factors; C091774:POU3F4 protein, human