title: Novel mutation in AAA domain of BCS1L causing Bjornstad syndrome.
abstract: Bjørnstad syndrome is an extremely rare condition characterized by pilitorti and nerve deafness. Only few large families have been reported worldwide. Here we describe a large Pakistani family with five affected individuals. The hair fibers of all the patients were twisted around their axis and devoid of any pigment. In addition the patients had a moderate-to-severe degree of hearing impairment. Genotyping with high-density single-nucleotide polymorphism arrays showed homozygosity in two intervals on chromosome 2. Linkage with one of these regions (genomic position 218745685-221025443, hg19) was confirmed. This region encompasses the BCS1L gene. Mutations in this gene have previously been associated with Bjørnstad's syndrome. We sequenced the BCS1L gene for identification of the causative mutation in the family. A novel homozygous missense mutation c.901T>A was identified, which segregated with the disease in the family. This mutation results in the amino acid change p.Tyr301Asn and was predicted to be pathogenic by bioinformatics tools.
authors.affiliation: Institute of Biomedical and Genetic Engineering (IBGE), Islamabad, Pakistan.
authors.forename: Saima
authors.initials: S
authors.lastname: Siddiqi
authors.affiliation: National Institute of Handicap, Islamabad, Pakistan.
authors.forename: Saadat
authors.initials: S
authors.lastname: Siddiq
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, Nijmegen, The Netherlands [2] Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands [3] Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
authors.forename: Jaap
authors.initials: J
authors.lastname: Oostrik
authors.affiliation: Institute of Biomedical and Genetic Engineering (IBGE), Islamabad, Pakistan.
authors.forename: Nafees
authors.initials: N
authors.lastname: Ahmad
authors.affiliation: Institute of Biomedical and Genetic Engineering (IBGE), Islamabad, Pakistan.
authors.forename: Syed Ali Raza
authors.initials: SA
authors.lastname: Kazmi
authors.affiliation: 1] Department of Otorhinolaryngology, Head and Neck Surgery, Nijmegen, The Netherlands [2] Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands [3] Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands [4] Department of Human Genetics, Radboud University Nijmegen Medical Centre, 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, Nijmegen, The Netherlands [2] Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands [3] Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
authors.forename: Margit
authors.initials: M
authors.lastname: Schraders
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D002648:Child; D014450:Electron Transport Complex III / Q000235:genetics*; D005260:Female; D005838:Genotype; D006201:Hair Diseases / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000151:congenital* / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D010154:Pakistan; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: C435491:BCS1L protein, human; D000074183:ATPases Associated with Diverse Cellular Activities; D014450:Electron Transport Complex III