title: A canonical splice site mutation in GIPC3 causes sensorineural hearing loss in a large Pakistani family.
abstract: With homozygosity mapping we have identified two large homozygous regions on chromosome 3q13.11-q13.31 and chromosome 19p13.3-q31.32 in a large Pakistani family suffering from autosomal recessive nonsyndromic hearing impairment (arNSHI). The region on chromosome 19 overlaps with the previously described deafness loci DFNB15, DFNB72 and DFNB95. Mutations in GIPC3 have been shown to underlie the nonsyndromic hearing impairment linked to these loci. Sequence analysis of all exons and exon-intron boundaries of GIPC3 revealed a homozygous canonical splice site mutation, c.226-1G>T, in GIPC3. This is the first mutation described in GIPC3 that affects splicing. The c.226-1G>T mutation is located in the acceptor splice site of intron 1 and is predicted to affect the normal splicing of exon 2. With a minigene assay it was shown to result in the use of an alternative acceptor site in exon 2, resulting in a frameshift and a premature stop codon. This study expands the mutational spectrum of GIPC3 in arNSHI.
authors.affiliation: Institute of Biomedical and Genetic Engineering (IBGE), Islamabad, Pakistan.
authors.forename: Saima
authors.initials: S
authors.lastname: Siddiqi
authors.affiliation: Institute of Biomedical and Genetic Engineering (IBGE), Islamabad, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ismail
authors.affiliation: 1] Department of Otorhinolaryngology, Head and Neck Surgery, Radboud University Medical Center, Nijmegen, The Netherlands [2] Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Jaap
authors.initials: J
authors.lastname: Oostrik
authors.affiliation: 1] Institute of Biomedical and Genetic Engineering (IBGE), Islamabad, Pakistan [2] Research Center For Modeling and Simulation, National University of Sciences and Technology (NUST), Islamabad, Pakistan.
authors.forename: Saba
authors.initials: S
authors.lastname: Munawar
authors.affiliation: Institute of Biomedical and Genetic Engineering (IBGE), Islamabad, Pakistan.
authors.forename: Atika
authors.initials: A
authors.lastname: Mansoor
authors.affiliation: 1] Department of Otorhinolaryngology, Head and Neck Surgery, Radboud University Medical Center, Nijmegen, The Netherlands [2] Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands [3] Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Hannie
authors.initials: H
authors.lastname: Kremer
authors.affiliation: 1] COMSATS Institute of Information Technology, Islamabad, Pakistan [2] Al-Nafees Medical College and Hospital, Isra University, Islamabad, Pakistan.
authors.forename: Raheel
authors.initials: R
authors.lastname: Qamar
authors.affiliation: 1] Department of Otorhinolaryngology, Head and Neck Surgery, Radboud University Medical Center, Nijmegen, The Netherlands [2] Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Margit
authors.initials: M
authors.lastname: Schraders
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000235:genetics*; D008040:Genetic Linkage; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000473:pathology; D006801:Humans; D009154:Mutation; D010154:Pakistan; D010375:Pedigree; D022821:RNA Splice Sites / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C452600:GIPC3 protein, human; D022821:RNA Splice Sites