Identification and functional characterization of a novel splicing mutation in RP gene PRPF31.
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.
Liu
Jing Yu
JY
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.
Dai
Xiaohua
X
Sheng
Jiqun
J
Cui
Xin
X
Wang
Xu
X
Jiang
Xueqing
X
Tu
Xin
X
Tang
Zhaohui
Z
Bai
Yan
Y
Liu
Mugen
M
Wang
Qing K
QK
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*
D005136:Eye Proteins; C454222:PRPF31 protein, human