title: Splice-site mutations in the TRIC gene underlie autosomal recessive nonsyndromic hearing impairment in Pakistani families.
abstract: Hereditary hearing impairment (HI) displays extensive genetic heterogeneity. To date, 67 autosomal recessive nonsyndromic hearing impairment (ARNSHI) loci have been mapped, and 24 genes have been identified. This report describes three large consanguineous ARNSHI Pakistani families, all of which display linkage to marker loci located in the genetic interval of DFNB49 locus on chromosome 5q13. Recently, Riazuddin et al. (Am J Hum Genet 2006; 79:1040-1051) reported that variants within the TRIC gene, which encodes tricellulin, are responsible for HI due to DFNB49. TRIC gene sequencing in these three families led to the identification of a novel mutation (IVS4+1G> A) in one family and the discovery of a previously described mutation (IVS4+2T> C) in two families. It is estimated that 1.06% (95% confidence interval 0.02-3.06%) of families with ARNSHI in Pakistan manifest HI due to mutations in the TRIC gene.
authors: Department of Biochemistry, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad, Pakistan.
authors: Muhammad S
authors: MS
authors: Chishti
authors: Department of Biochemistry, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad, Pakistan.
authors: Attya
authors: A
authors: Bhatti
authors: Department of Biochemistry, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad, Pakistan.
authors: Sana
authors: S
authors: Tamim
authors: Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Alkek Building N1619.01, Houston, TX, 77030, USA.
authors: Kwanghyuk
authors: K
authors: Lee
authors: Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Alkek Building N1619.01, Houston, TX, 77030, USA.
authors: Merry-Lynn
authors: ML
authors: McDonald
authors: Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Alkek Building N1619.01, Houston, TX, 77030, USA.
authors: Suzanne M
authors: SM
authors: Leal
authors: Department of Biochemistry, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad, Pakistan. wahmad@qau.edu.pk.
authors: Wasim
authors: W
authors: Ahmad
mesh_terms: D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005260:Female; D005808:Genes, Recessive / Q000235:genetics*; D008040:Genetic Linkage; D005838:Genotype; D034381:Hearing Loss / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D062794:MARVEL Domain Containing 2 Protein; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010154:Pakistan; D010375:Pedigree; D016133:Polymerase Chain Reaction; D022821:RNA Splice Sites / Q000235:genetics*; D019108:Tight Junctions
chemical_list: D062794:MARVEL Domain Containing 2 Protein; C516798:MARVELD2 protein, human; D008565:Membrane Proteins; D022821:RNA Splice Sites