title: Exome Sequencing Reveals AGBL5 as Novel Candidate Gene and Additional Variants for Retinitis Pigmentosa in Five Turkish Families.
abstract: OBJECTIVE
  Retinitis pigmentosa (RP) is the most common inherited retinal disease with high genetic heterogeneity and variable phenotypes. Characteristic symptoms include night blindness and progressive loss of visual field, leading to blindness. Mutations in >60 genes have been identified to date as causative for RP, and additional candidate genes are assumed.
  
  
  METHODS
  To find the disease-causing mutations in the affected members of five Turkish families, we sequenced whole exomes using an Illumina platform.
  
  
  RESULTS
  Among all candidate genes for retinal degeneration we found two previously known sequence variations: a 4 bp deletion in the RPGR gene (c.1662_1665delAGAA; p.Glu555Glyfs*14) and a recently described USH1-causing missense mutation in MYO7A (c.472G>A, p.Gly158Arg). Furthermore, a novel 1 bp deletion in the VCAN gene (c.5118delA; p.Ser1707Valfs*44) was detected as well as a large deletion in EYS, spanning ∼ 400kb and comprising exons 16-26 (p.fs*). In one family, exome analyses of two affected individuals revealed a homozygous missense mutation (c.883G>A; p.Asp295Asn) in the AGBL5 (Agbl5; CCP5) gene, previously not reported to be associated with RP. RNA and protein analyses showed expression in human retina, as well as in mouse retina, brain and testis. Furthermore, cDNA analyses indicate the existence of tissue-specific AGBL5 splice variations in humans. AGBL5/CCP5 immunoreactivity was also visualized in human and mouse retinae.
  
  
  CONCLUSIONS
  Due to the characteristic RP phenotype in patients carrying the AGBL5 missense mutation we suggest this gene as a candidate for a new form of autosomal recessively inherited RP and recommend further investigation to confirm this hypothesis.
authors.affiliation: Ruhr-University Bochum, Human Genetics, Bochum, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Kastner
authors.affiliation: Ruhr-University Bochum, Human Genetics, Bochum, Germany.
authors.forename: Ina-Janine
authors.initials: IJ
authors.lastname: Thiemann
authors.affiliation: Ruhr-University Bochum, Human Genetics, Bochum, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Dekomien
authors.affiliation: Ruhr-University Bochum, Neuroanatomy and Molecular Brain Research, Bochum, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Petrasch-Parwez
authors.affiliation: Ruhr-University Bochum, Human Genetics, Bochum, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Schreiber
authors.affiliation: Ruhr-University Bochum, Human Genetics, Bochum, Germany.
authors.forename: Denis A
authors.initials: DA
authors.lastname: Akkad
authors.affiliation: Ruhr-University Bochum, Human Genetics, Bochum, Germany.
authors.forename: Wanda M
authors.initials: WM
authors.lastname: Gerding
authors.affiliation: Ruhr-University Bochum, Human Genetics, Bochum, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Hoffjan
authors.affiliation: Ondokuz Mayis University, Faculty of Medicine, Department of Medical Biology, Samsun, Turkey.
authors.forename: Sezgin
authors.initials: S
authors.lastname: Günes
authors.affiliation: Samsun Education and Research Hospital, Department of Ophthalmology, Samsun, Turkey.
authors.forename: Selçuk
authors.initials: S
authors.lastname: Günes
authors.affiliation: Ondokuz Mayis University, Faculty of Medicine, Department of Medical Biology, Samsun, Turkey.
authors.forename: Hasan
authors.initials: H
authors.lastname: Bagci
authors.affiliation: Ruhr-University Bochum, Human Genetics, Bochum, Germany 5University Witten/Herdecke, Faculty of Health, Witten, Germany.
authors.forename: Jörg T
authors.initials: JT
authors.lastname: Epplen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002268:Carboxypeptidases / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D059472:Exome / Q000235:genetics*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D020125:Mutation, Missense; D047728:Myopia, Degenerative / Q000235:genetics*; D010375:Pedigree; D012174:Retinitis Pigmentosa / Q000235:genetics*; D014421:Turkey
chemical_list: C000607347:AGBL5 protein, human; D002268:Carboxypeptidases