Original Article
Novel mutations in the TULP1 and CNGB1 genes in a family affected with early onset severe retinal dystrophy
Wei Yuanmeng, Li Miao, Peng Haiying, Zhou Zhongqiang, Tang He, Shi Pingling, Liang Yingjuan, Tian Meizhi
Published 2021-01-25
Cite as Chin J Ocul Fundus Dis, 2021, 37(1): 47-53. DOI: 10.3760/cma.j.cn511434-20200427-00182
Abstract
ObjectiveTo identify the pathogenic gene mutations in a family with early onset severe retinal dystrophy (EOSRD).
MethodsA retrospective clinical study. One patient and three family members from a Han of EOSRD who were diagnosed at Henan Eye Hospital in August 2018 were included in the study. After the detailed history of the patients was collected, all participants underwent best corrected visual acuity (BCVA), slit-lamp, fundus biomicroscopy with the slit lamp, untra-widefield fundus color photography, spectral-domain optical coherence tomography (SD-OCT) and full-field electroretinography (ff-ERG). The subject’s peripheral venous blood of 5 ml was collected and the whole genome DNA was extracted. A genetic eye disease capture chip containing 441 disease-causing genes was used for targeted capture and enrichment of high-throughput sequencing, and Sanger sequencing was performed for the clear pathogenic mutation sites; the analysis software was used for bioinformatics analysis of the mutation sites.
ResultsA 6-year-old female proband developed poor night vision in both eyes after 1 year old. The BCVA of both eyes were 0.1. The color of the optic disc was slightly lighter; the diameter of the retinal vessels was slightly reduced, and extensive pigment changes can be seen in the retina outside the vascular arch. SD-OCT examination showed that the outer membrane, ellipsoid zone and chimera zone in the central fovea of both eyes were unclear and intermittent. The visual area outside the fovea was neuroepithelial outer plexiform layer, outer nuclear layer, outer membrane, ellipsoid zone. The chimera zone gradually disappeared, and the thickness of the pigment epithelial layer was not uniform. In ff-ERG examination, the functions of the binocular cone and rod system were severely decreased. The results of genetic testing showed that there were c.921C>A homozygous mutations in the Tubby-like protein (TULP1) gene of the proband, and c.3121C>T and c.3488G>A compound heterozygous mutations in the cyclic nucleotide gated channel beta 1 (CNGB1) gene. Amino acid conservation analysis results showed that the above three mutation sites were highly conserved in multiple species; bioinformatics analysis results showed that TULP1 gene c.921C>A (p.Cys307*) had translation termination in the protein conserved region, CNGB1 gene c.3121C>T (p.Arg1041Trp) and c.3488G>A (p.Gly1163Glu) had amino acid polarity changes in the protein conserved region, which led to major changes in the protein spatial structure.
ConclusionTULP1 gene c.921C>A homozygous mutation, CNGB1 gene c.3121C>T and c.3488G>A compound heterozygous mutation are the mutation sites of this EOSRD family.
Key words:
Retinal dystrophy; Gene; Mutation; TULP1 gene; CNGB1 gene
Contributor Information
Wei Yuanmeng
Henan Eye Institute, Henan Eye Hospital, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou 450003, China
Li Miao
Henan Eye Institute, Henan Eye Hospital, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou 450003, China
Peng Haiying
Henan Eye Institute, Henan Eye Hospital, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou 450003, China
Zhou Zhongqiang
Henan Eye Institute, Henan Eye Hospital, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou 450003, China
Tang He
Henan Eye Institute, Henan Eye Hospital, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou 450003, China
Shi Pingling
Henan Eye Institute, Henan Eye Hospital, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou 450003, China
Liang Yingjuan
Henan Eye Institute, Henan Eye Hospital, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou 450003, China
Tian Meizhi
Henan Eye Institute, Henan Eye Hospital, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou 450003, China
Tian Meizhi is now working at Luyi County Eye Hospital, Zhoukou 477200, China
