title: Identification and functional characterization of a novel splicing mutation in RP gene PRPF31.
abstract: A six-generation Chinese family with autosomal dominant retinitis pigmentosa (adRP) was identified and characterized. Genome-wide linkage analysis linked the family to markers D19S601 to D19S605, which span the PRPF31 gene on chromosome 19q13.33-13.43 (RP11) (LOD=5.03). Direct DNA sequence analysis identified a novel splicing mutation (IVS1+1G>T) in affected family members and carriers, but not in unaffected family members and 200 normal controls. The splicing mutation occurs at the splicing donor of intron 1. Real time PCR with lymphoblastoid RNA samples from family members showed that in comparison to normal family members, the splicing mutation reduced the expression level of the PRPF31 mRNA by 57% in symptomatic patients and by 28% in clinically asymptomatic carriers. Our studies identify a novel splicing mutation in PRPF31 associated with adRP and suggest that the penetrance of RP11 mutations may be correlated with the expression level of the PRPF31 mRNA.
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, PR China.
authors.forename: Jing Yu
authors.initials: JY
authors.lastname: Liu
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Dai
authors.forename: Jiqun
authors.initials: J
authors.lastname: Sheng
authors.forename: Xin
authors.initials: X
authors.lastname: Cui
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.forename: Xueqing
authors.initials: X
authors.lastname: Jiang
authors.forename: Xin
authors.initials: X
authors.lastname: Tu
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Tang
authors.forename: Yan
authors.initials: Y
authors.lastname: Bai
authors.forename: Mugen
authors.initials: M
authors.lastname: Liu
authors.forename: Qing K
authors.initials: QK
authors.lastname: Wang
mesh_terms: D025063:Chromosome Disorders / Q000235:genetics*; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D019154:Protein Splicing / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000235:genetics*
chemical_list: D005136:Eye Proteins; C454222:PRPF31 protein, human