title: Deep intronic GPR143 mutation in a Japanese family with ocular albinism.
abstract: Deep intronic mutations are often ignored as possible causes of human disease. Using whole-exome sequencing, we analysed genomic DNAs of a Japanese family with two male siblings affected by ocular albinism and congenital nystagmus. Although mutations or copy number alterations of coding regions were not identified in candidate genes, the novel intronic mutation c.659-131 T > G within GPR143 intron 5 was identified as hemizygous in affected siblings and as heterozygous in the unaffected mother. This mutation was predicted to create a cryptic splice donor site within intron 5 and activate a cryptic acceptor site at 41nt upstream, causing the insertion into the coding sequence of an out-of-frame 41-bp pseudoexon with a premature stop codon in the aberrant transcript, which was confirmed by minigene experiments. This result expands the mutational spectrum of GPR143 and suggests the utility of next-generation sequencing integrated with in silico and experimental analyses for improving the molecular diagnosis of this disease.
authors.affiliation: Department of Stress Science, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Naruto
authors.affiliation: Department of Medical Genetics, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi 594-1101, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Okamoto
authors.affiliation: Department of Human Genetics, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Masuda
authors.affiliation: Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita 565-0871, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Endo
authors.affiliation: Eye Department, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi 594-1101, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Hatsukawa
authors.affiliation: 1] Department of Human Genetics, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan [2] Student Lab, Tokushima University Faculty of Medicine, Tokushima 770-8503, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kohmoto
authors.affiliation: Department of Human Genetics, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan.
authors.forename: Issei
authors.initials: I
authors.lastname: Imoto
mesh_terms: D016117:Albinism, Ocular / Q000175:diagnosis / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002648:Child; D018389:Codon, Nonsense / Q000235:genetics*; D059472:Exome / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D007438:Introns / Q000235:genetics; D007564:Japan; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D020417:Nystagmus, Congenital / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D018389:Codon, Nonsense; D005136:Eye Proteins; C095276:GPR143 protein, human; D008562:Membrane Glycoproteins