[Splicing site mutation of D19S418 in PRPF-31 gene and its phenotypic characters with autosomal dominant retinitis pigmentosa].
OBJECTIVE
To evaluate the disease-causing gene and phenotypic characters of a large family with autosomal dominant retinitis pigmentosa (adRP).


METHODS
Disease status and associated ocular abnormalities of eight patients and six unaffected members who represent different generations of this family were assessed by measurement of visual psychophysics, full-field and multifocal electrophysiology (ERG and mfERG) and funds fluorescent angiography (FFA). The DNA samples of nineteen patients and fifteen unaffected individuals in this family were examined by Genome scanning, linkage analysis and mutation detection to identify coding sequence changes.


RESULTS
A case with variable, early onset night blindness before 10 years and visual field loss in their teens was found. Macular dystrophy, progressing to a retinitis pigmentosa phenotype was demonstrated in most adult cases. Both a-wave and b-wave amplitudes of photopic and scotopic full-field ERG were marked reduced and nearly non-detectable, demonstrating severe damage of photoreceptor systems. There were two obligate gene carriers in the family which remained asymptomatic in the clinical. But one of them was found with a minimal RP characteristic and the other was normal by examination of fundus and ERG. An unreported splicing site mutation (IVS5-1G > A) was identified in intron 5- acceptor site of PRPF-31 gene on chromosome 19. ERG and molecular genetic findings were consistent with the reclassification of this disease as an autosomal dominant RP.


CONCLUSIONS
It is a novel splicing site mutation that IVS5-1G > A of D19S418 site in PRFP31, the relative phenotypes by which main displayed type I/diffuse has variable expressivity and complex phenotype.
Xi
Xing-hua
XH
Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha 410011, China. xhx96@yahoo.com.cn
Zheng
Duo
D
Xia
Kun
K
Pan
Qian
Q
Lei
Lu-yun
LY
Liu
Zheng
Z
Tang
Chao-zhen
CZ
Xia
Jia-hui
JH
Jiang
De-yong
DY
Deng
Han-xiang
HX
D000293:Adolescent; D000328:Adult; D002648:Child; D025063:Chromosome Disorders / Q000235:genetics*; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D022821:RNA Splice Sites / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000235:genetics*; D055815:Young Adult
D005136:Eye Proteins; C454222:PRPF31 protein, human; D022821:RNA Splice Sites