OBJECTIVE: To identify the gene causing retinitis pigmentosa (RP) in an autosomal dominant pedigree. METHODS: Family members with RP were studied with linkage analysis using single-nucleotide polymorphism and short tandem repeat polymorphic markers. Candidate genes in the linked region were evaluated with DNA sequencing. RESULTS: Nineteen family members had a mild form of RP. Multipoint linkage analysis of single-nucleotide polymorphism genotypes yielded a maximum nonparametric linkage score of 19.97 with markers located on chromosome 14q. LOD scores higher than 3.0 were obtained with 20 short tandem repeat polymorphic markers, and recombinants defined a 21.7-centimorgan locus on chromosome 14q. The retinol dehydrogenase 12 (RDH12) gene lies within this locus and was evaluated as a candidate gene. A frameshift mutation (776delG) was detected in all affected family members and was not detected in 158 control subjects. CONCLUSIONS: Heterozygous mutations in RDH12 can cause autosomal dominant RP with a late onset and relatively mild severity. This phenotype is dramatically different from the other disease associated with mutation in this gene, autosomal recessive Leber congenital amaurosis. CLINICAL RELEVANCE: The demonstration that mutations in a gene previously associated with recessive Leber congenital amaurosis can also cause dominant RP illustrates the wide phenotypic variability of retinal degeneration genes.
OBJECTIVE: To identify the gene causing retinitis pigmentosa (RP) in an autosomal dominant pedigree. METHODS: Family members with RP were studied with linkage analysis using single-nucleotide polymorphism and short tandem repeat polymorphic markers. Candidate genes in the linked region were evaluated with DNA sequencing. RESULTS: Nineteen family members had a mild form of RP. Multipoint linkage analysis of single-nucleotide polymorphism genotypes yielded a maximum nonparametric linkage score of 19.97 with markers located on chromosome 14q. LOD scores higher than 3.0 were obtained with 20 short tandem repeat polymorphic markers, and recombinants defined a 21.7-centimorgan locus on chromosome 14q. The retinol dehydrogenase 12 (RDH12) gene lies within this locus and was evaluated as a candidate gene. A frameshift mutation (776delG) was detected in all affected family members and was not detected in 158 control subjects. CONCLUSIONS: Heterozygous mutations in RDH12 can cause autosomal dominant RP with a late onset and relatively mild severity. This phenotype is dramatically different from the other disease associated with mutation in this gene, autosomal recessive Leber congenital amaurosis. CLINICAL RELEVANCE: The demonstration that mutations in a gene previously associated with recessive Leber congenital amaurosis can also cause dominant RP illustrates the wide phenotypic variability of retinal degeneration genes.
Authors: Hilda Petrs-Silva; Douglas Yasumura; Michael T Matthes; Matthew M LaVail; Alfred S Lewin; William W Hauswirth Journal: Adv Exp Med Biol Date: 2012 Impact factor: 2.622
Authors: Xia Wang; Hui Wang; Ming Cao; Zhe Li; Xianfeng Chen; Claire Patenia; Athurva Gore; Emad B Abboud; Ali A Al-Rajhi; Richard A Lewis; James R Lupski; Graeme Mardon; Kun Zhang; Donna Muzny; Richard A Gibbs; Rui Chen Journal: Hum Mutat Date: 2011-09-23 Impact factor: 4.878