A novel mutation in the RPE65 gene causing Leber congenital amaurosis and its transcriptional expression in vitro.
The retinal pigment epithelium-specific 65 kDa protein is an isomerase encoded by the RPE65 gene (MIM 180069) that is responsible for an essential enzymatic step required for the function of the visual cycle. Mutations in the RPE65 gene cause not only subtype II of Leber congenital amaurosis (LCA) but also early-onset severe retinal dystrophy (EOSRD). This study aims to investigate a Chinese case diagnosed as EOSRD and to characterize the polymorphisms of the RPE65 gene. A seven-year-old girl with clinical symptoms of EOSRD and her parents were recruited into this study. Ophthalmologic examinations, including best-corrected visual acuity, slit-lamp, Optical coherence tomography (OCT), and fundus examination with dilated pupils, were performed to determine the clinical characteristics of the whole family. We amplified and sequenced the entire coding region and adjacent intronic sequences of the coding regions of the RPE65 gene for the whole family to explore the possible mutation. Our results demonstrate that the patient exhibited the typical clinically features of EOSRD. Her bilateral decimal visual acuity was 0.3 and 0.4 in the left and right eyes, respectively. Spectral-domain optical coherence tomography (SD-OCT) was used to assess the retinal stratification for the whole family. All together, we identified four mutations within the RPE65 gene (c.1056G>A, c.1243+2T>A, c.1338+20A>C and c.1590C>A) in the patient. Among the four mutations, c.1056G>A and c.1338+20A>C had been reported previously and another two were found for the first time in this study. Her mother also carried the novel mutation (c.1243+2T>A). Either a single or a compound heterozygous or a homozygous one mutation is expected to cause EOSRD because mutations of RPE65 gene usually cause an autosomal recessive disease. Therefore, we speculate that the c.1590C>A mutation together with the c.1243+2T>A mutation may cause the patient's phenotype.
China Key Laboratory of TCM Resource and Prescription, Hubei University of Chinese Medicine, Ministry of Education, Wuhan 430065, China.
Guoyan
G
Mo
Department of Ophthalmology, Wuhan General Hospital of Guangzhou Military Command, Wuhan 430070, China.
Qin
Q
Ding
Department of Ophthalmology, Wuhan General Hospital of Guangzhou Military Command, Wuhan 430070, China.
Zhongshan
Z
Chen
Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing 100029, China.
Yunbo
Y
Li
Department of Ophthalmology, Wuhan General Hospital of Guangzhou Military Command, Wuhan 430070, China.
Ming
M
Yan
Department of Biology, University of New Mexico, Albuquerque, NM, 87131, United States of America.
Lijing
L
Bu
Department of Ophthalmology, Wuhan General Hospital of Guangzhou Military Command, Wuhan 430070, China.
Yanping
Y
Song
Department of Plant Biology and Pathology, Rutgers, The State University of New Jersey, New Brunswick, NJ, 08901, United States of America; Wuhan Sheng Da An Biotech Service Co. Ltd., Wuhan, China.
Guohua
G
Yin
D044466:Asian People / Q000235:genetics*; D002648:Child; D002681:China; D005260:Female; D056726:Genetic Association Studies; D057809:HEK293 Cells; D006801:Humans; D066298:In Vitro Techniques; D057130:Leber Congenital Amaurosis / Q000235:genetics* / Q000473:pathology*; D008297:Male; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism; D017422:Sequence Analysis, DNA; D019745:cis-trans-Isomerases / Q000235:genetics*; D000099178:Retinoid Isomerohydrolase
D012333:RNA, Messenger; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase