title: Identification of missense mutation (I12T) in the BSND gene and bioinformatics analysis.
abstract: Nonsyndromic hearing loss is a paradigm of genetic heterogeneity with 85 loci and 39 nuclear disease genes reported so far. Mutations of BSND have been shown to cause Bartter syndrome type IV, characterized by significant renal abnormalities and deafness and nonsyndromic nearing loss. We studied a Pakistani consanguineous family. Clinical examinations of affected individuals did not reveal the presence of any associated signs, which are hallmarks of the Bartter syndrome type IV. Linkage analysis identified an area of 18.36 Mb shared by all affected individuals between markers D1S2706 and D1S1596. A maximum two-point LOD score of 2.55 with markers D1S2700 and multipoint LOD score of 3.42 with marker D1S1661 were obtained. BSND mutation, that is, p.I12T, cosegregated in all extant members of our pedigree. BSND mutations can cause nonsyndromic hearing loss, and it is a second report for this mutation. The respected protein, that is, BSND, was first modeled, and then, the identified mutation was further analyzed by using different bioinformatics tools; finally, this protein and its mutant was docked with CLCNKB and REN, interactions of BSND, respectively.
authors.affiliation: Department of Bioinformatics and Biotechnology, International Islamic University, Islamabad, Pakistan.
authors.forename: Hina
authors.initials: H
authors.lastname: Iqbal
authors.forename: Tayyba
authors.initials: T
authors.lastname: Sarfaraz
authors.forename: Farida
authors.initials: F
authors.lastname: Anjum
authors.forename: Zubair
authors.initials: Z
authors.lastname: Anwar
authors.forename: Asif
authors.initials: A
authors.lastname: Mir
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D018118:Chloride Channels / Q000737:chemistry / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D019295:Computational Biology / Q000379:methods*; D017124:Conserved Sequence / Q000235:genetics; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D006239:Haplotypes / Q000235:genetics; D006319:Hearing Loss, Sensorineural / Q000235:genetics; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D055815:Young Adult
chemical_list: C440005:BSND protein, human; D018118:Chloride Channels