Exome sequencing identifies compound heterozygous mutations in CYP4V2 in a pedigree with retinitis pigmentosa.
Retinitis pigmentosa (RP) is a heterogeneous group of progressive retinal degenerations characterized by pigmentation and atrophy in the mid-periphery of the retina. Twenty two subjects from a four-generation Chinese family with RP and thin cornea, congenital cataract and high myopia is reported in this study. All family members underwent complete ophthalmologic examinations. Patients of the family presented with bone spicule-shaped pigment deposits in retina, retinal vascular attenuation, retinal and choroidal dystrophy, as well as punctate opacity of the lens, reduced cornea thickness and high myopia. Peripheral venous blood was obtained from all patients and their family members for genetic analysis. After mutation analysis in a few known RP candidate genes, exome sequencing was used to analyze the exomes of 3 patients III2, III4, III6 and the unaffected mother II2. A total of 34,693 variations shared by 3 patients were subjected to several filtering steps against existing variation databases. Identified variations were verified in the rest family members by PCR and Sanger sequencing. Compound heterozygous c.802-8_810del17insGC and c.1091-2A>G mutations of the CYP4V2 gene, known as genetic defects for Bietti crystalline corneoretinal dystrophy, were identified as causative mutations for RP of this family.
Ophthalmic Laboratories & Department of Ophthalmology, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People's Republic of China.
Yun
Y
Wang
Liheng
L
Guo
Su-Ping
SP
Cai
Meizhi
M
Dai
Qiaona
Q
Yang
Wenhan
W
Yu
Naihong
N
Yan
Xiaomin
X
Zhou
Jin
J
Fu
Xinwu
X
Guo
Pengfei
P
Han
Jun
J
Wang
Xuyang
X
Liu
D001483:Base Sequence; D002386:Cataract / Q000150:complications / Q000235:genetics; D002648:Child; D003315:Cornea / Q000473:pathology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D000072470:Cytochrome P450 Family 4; D005091:Exons / Q000235:genetics*; D005260:Female; D023281:Genomics; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009216:Myopia / Q000150:complications; D010375:Pedigree; D012174:Retinitis Pigmentosa / Q000150:complications / Q000235:genetics* / Q000473:pathology; D017422:Sequence Analysis, DNA
D003577:Cytochrome P-450 Enzyme System; C505357:CYP4V2 protein, human; D000072470:Cytochrome P450 Family 4