PURPOSE: To describe a hierarchical approach for efficient genetic diagnosis of autosomal dominant retinitis pigmentosa (adRP). METHODS: Forty di-, tri-, or tetra-nucleotide repeats tightly linked to 10 genes known to be responsible for adRP were identified from the human genome sequence and used as markers in multiplex amplification and genotyping, followed by linkage analysis. Discordance of cosegregation of markers and the disease excluded the majority of the examined genes as candidates, and mutation screening for the remaining genes was performed. RESULTS: With this strategy, examination of an adRP-affected family indicated that 3 of 10 candidate genes segregated concordantly with the disease. Further searches for mutations revealed a novel insertion and deletion in the last exon of a splicing factor gene, PRPF8. CONCLUSIONS: This systematic approach facilitates the molecular diagnosis of adRP, which is known to have a highly heterogeneous genetic background.
PURPOSE: To describe a hierarchical approach for efficient genetic diagnosis of autosomal dominant retinitis pigmentosa (adRP). METHODS: Forty di-, tri-, or tetra-nucleotide repeats tightly linked to 10 genes known to be responsible for adRP were identified from the human genome sequence and used as markers in multiplex amplification and genotyping, followed by linkage analysis. Discordance of cosegregation of markers and the disease excluded the majority of the examined genes as candidates, and mutation screening for the remaining genes was performed. RESULTS: With this strategy, examination of an adRP-affected family indicated that 3 of 10 candidate genes segregated concordantly with the disease. Further searches for mutations revealed a novel insertion and deletion in the last exon of a splicing factor gene, PRPF8. CONCLUSIONS: This systematic approach facilitates the molecular diagnosis of adRP, which is known to have a highly heterogeneous genetic background.
Authors: Daniel Mordes; Xiaoyan Luo; Amar Kar; David Kuo; Lili Xu; Kazuo Fushimi; Guowu Yu; Paul Sternberg; Jane Y Wu Journal: Mol Vis Date: 2006-10-26 Impact factor: 2.367
Authors: Kum-Loong Boon; Richard J Grainger; Parastoo Ehsani; J David Barrass; Tatsiana Auchynnikava; Chris F Inglehearn; Jean D Beggs Journal: Nat Struct Mol Biol Date: 2007-10-14 Impact factor: 15.369
Authors: Lenka Ivings; Katherine V Towns; M A Matin; Charles Taylor; Frederique Ponchel; Richard J Grainger; Rajkumar S Ramesar; David A Mackey; Chris F Inglehearn Journal: Mol Vis Date: 2008-12-18 Impact factor: 2.367