title: Detection of CRB1 mutations in families with retinal dystrophy through phenotype-oriented mutational screening.
abstract: Mutations in the crumbs homolog (CRB)1 gene are among the common causes of severe early onset retinal dystrophy. Some characteristic clinical phenotypes are frequently associated with mutations in CRB1. The aim of this study was to examine whether characteristic phenotype-directed mutational screening facilitated the detection of CRB1 mutations. The study included 22 probands with at least one of the potential CRB1-associated phenotypes for retinal dystrophy. Variants were detected using Sanger sequencing. The complete sequences of the coding and adjacent intronic regions of CRB1 were analyzed, revealing homozygous or compound heterozygous mutations in CRB1 in seven of 22 probands, involving six novel (c.136delA, c.1841G>T, c.3017C>A, c.3488G>T, c.3991C>T and c.4089dupTGTTGCTT) and four known (c.2222T>C, c.2671T>G, c.3676G>T and c.4005+2T>G) mutations. The mutations were present in three of four probands with macular nummular pigmentation and in four of seven probands with early onset retinitis pigmentosa with macular involvement. The results suggested that macular nummular pigmentation is a gene-specific indication for CRB1‑associated retinal dystrophy and confirm that CRB1 mutations are also common causes of early onset retinitis pigmentosa. Identification of gene-specific phenotypes is uselful in identifying genetic defects underlying heterogeneous retinal dystrophy.
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat‑sen University, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Shiqiang
authors.initials: S
authors.lastname: Li
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat‑sen University, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat‑sen University, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Xueshan
authors.initials: X
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat‑sen University, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Xiangming
authors.initials: X
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat‑sen University, Guangzhou, Guangdong 510060, P.R. China.
authors.forename: Qingjiong
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics*; D005190:Family; D005260:Female; D005654:Fundus Oculi; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D058499:Retinal Dystrophies / Q000235:genetics*; D055815:Young Adult
chemical_list: C448939:CRB1 protein, human; D005136:Eye Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins