Clinical and molecular genetic study of a Chinese Han family with X-linked retinoschisis

Wang Tingting,  Zhu Yihua,  Fan Mengjie,  Luo Xiaoling,  Zhang Linyan,  Zhang Daren,  Ding Xiaoyan,  Liu Xuyang
DOI: 10.3760/cma.j.cn115989-20210922-00523
Published 2023-09-10
Cite as Chin J Exp Ophthalmol, 2023, 41(9): 864-870.

Abstract                            【Download PDF】 【Read Full Text

Objective

To study the clinical phenotype and molecular genetic characteristics of a Chinese Han family with X-linked retinoschisis (XLRS), and to determine the associated gene variations.

Methods

A pedigree investigation was performed.The clinical characteristics and pedigree analysis of a Han Chinese family line with XLRS was conducted in August 2021 at the Xiamen Eye Center Affiliated to Xiamen University.All patients and the carriers underwent comprehensive medical history collection and routine ophthalmological examinations, including visual acuity, non-contact tonometer, slit lamp microscope, direct ophthalmoscope, and optical coherence tomography.The proband and some patients underwent medical optometry, fundus photography or wide-angle fundus photography, and electroretinogram examination.Peripheral venous blood samples were collected from the family members, and whole exome sequencing (WES) analysis was performed on the proband samples.For variants screened by WES, the expanded verification in other patients and normal persons in the family was carried out by Sanger sequencing.Multiple bioinformatic tools were used to analyze the pathogenicity of variants.This study protocol was approved by the Ethics Committee of Xiamen Eye Center of Xiamen University (No.XMYKZX-KY-2021-012). Written informed consent forms were obtained from each subject or guardian of minors.CADD, FATHMM and other bioinformatics tools were used to analyze the pathogenicity of the variation sites.

Results

The Han XLRS pedigree consisted of 8 individuals in 3 generations.Out of the 3 cases diagnosed with XLRS based on clinical evaluation, all were male.The mother of the proband was a carrier of related genes.There were 5 persons with normal phenotypes.There was no history of consanguineous marriages within the family, and the disease was shown to be intergenerational, which is consistent with the recessive inheritance of the X chromosome.None of the patients had a history of systemic disease or any other abnormal manifestations.The prevailing feature of ophthalmopathy was poor binocular vision since childhood.The proband and his younger brother had spoke split in the macula, and their grandfather showed atrophy of retinal nerve fibers.Genetic analysis revealed a hemizygous variation c. 214G>C: p.Glu72Gln in the RS1 gene in all the patients in this family.The proband’s mother was heterozygous at this site, and all other phenotypically normal family members exhibited wild type at this site.This variant was predicted to be a deleterious variation and likely to cause disease based on bioinformatics analysis.

Conclusions

The proband and patients in this Han Chinese family have the known c. 214G>C: p.Glu72Gln hemizygous variation of the RS1 gene and exhibit mild XLRS, which was consistent with the recessive inheritance of X chromosome.

Key words:

X-linked retinoschisis; Pedigree; RS1 gene; Genotype; Phenotype; Genetic analysis

Contributor Information

Wang Tingting

Xiamen Eye Center of Xiamen University, Xiamen 361000, China

Zhu Yihua

Department of Ophthalmology, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350004, China

Fan Mengjie

Department of Ophthalmology, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350004, China

Luo Xiaoling

Department of Ophthalmology, Shenzhen People’s Hospital, 2nd Clinical Medical College of Jinan University, Shenzhen 518040, China

Zhang Linyan

Zhongshan Ophthalmic Center of Sun Yat-sen University, Guangzhou 510060, China

Zhang Daren

Xiamen Eye Center of Xiamen University, Xiamen 361000, China

Ding Xiaoyan

Zhongshan Ophthalmic Center of Sun Yat-sen University, Guangzhou 510060, China

Liu Xuyang

Xiamen Eye Center of Xiamen University, Xiamen 361000, China

Department of Ophthalmology, Shenzhen People’s Hospital, 2nd Clinical Medical College of Jinan University, Shenzhen 518040, China

(Read 12 times, 1 visits today)