A novel PRPF31 mutation in a large Chinese family with autosomal dominant retinitis pigmentosa and macular degeneration.
OBJECTIVE
This study was intended to identify the disease causing genes in a large Chinese family with autosomal dominant retinitis pigmentosa and macular degeneration.


METHODS
A genome scan analysis was conducted in this family for disease gene preliminary mapping. Snapshot analysis of selected SNPs for two-point LOD score analysis for candidate gene filter. Candidate gene PRPF31 whole exons' sequencing was executed to identify mutations.


RESULTS
A novel nonsense mutation caused by an insertion was found in PRPF31 gene. All the 19 RP patients in 1085 family are carrying this heterozygous nonsense mutation. The nonsense mutation is in PRPF31 gene exon9 at chr19:54629961-54629961, inserting nucleotide "A" that generates the coding protein frame shift from p.307 and early termination at p.322 in the snoRNA binding domain (NOP domain).


CONCLUSIONS
This report is the first to associate PRPF31 gene's nonsense mutation and adRP and JMD. Our findings revealed that PRPF31 can lead to different clinical phenotypes in the same family, resulting either in adRP or syndrome of adRP and JMD. We believe our identification of the novel "A" insertion mutation in exon9 at chr19:54629961-54629961 in PRPF31 can provide further genetic evidence for clinical test for adRP and JMD.
Center for Human Molecular Biology & Genetics, The Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China ; Sichuan Translational Research Hospital, Chinese Academy of Sciences, Chengdu, Sichuan, China.
Fang
F
Lu
Lulin
L
Huang
Chuntao
C
Lei
Guiquan
G
Sha
Hong
H
Zheng
Xiaoqi
X
Liu
Jiyun
J
Yang
Yi
Y
Shi
Ying
Y
Lin
Bo
B
Gong
Xianjun
X
Zhu
Shi
S
Ma
Lifeng
L
Qiao
He
H
Lin
Jing
J
Cheng
Zhenglin
Z
Yang
D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People; D002681:China; D018389:Codon, Nonsense; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D017434:Protein Structure, Tertiary; D012174:Retinitis Pigmentosa / Q000235:genetics*
D018389:Codon, Nonsense; D005136:Eye Proteins; C454222:PRPF31 protein, human