Clinical characteristics and genetic analysis of a novel CACNA1F gene variant associated with cone-rod dystrophy
10.3760/cma.j.cn115989-20241008-00281
- VernacularTitle:视锥视杆细胞营养不良相关 CACNA1F基因新发变异的临床特征及遗传学分析
- Author:
Miao LI
1
;
Haiying PENG
1
;
He TANG
1
;
Zhongqiang ZHOU
1
;
Yuanmeng WEI
1
;
Pingling SHI
1
;
Yingjuan LIANG
1
Author Information
1. 河南省人民医院眼科 郑州大学人民医院眼科 河南省立眼科医院，郑州 450003
- Publication Type:Journal Article
- Keywords:
Mutation;
CACNA1F gene;
Cone-rod dystrophy
- From:
Chinese Journal of Experimental Ophthalmology
2025;43(9):827-832
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To identify the pathogenic gene in a family with cone-rod dystrophy (CRD).Methods:A pedigree study was conducted.Clinical data were collected from three generations of six people from a family with CRD who visited Henan Eye Hospital in December 2019, including one patient.After detailed collection of the patient's medical history, the proband and his family members underwent best-corrected visual acuity, slit-lamp microscope+ front-lens examination, optometry, non-mydriatic fundus photography, spectral-domain optical coherence tomography (SD-OCT), and full-field flash electroretinography (ff-ERG). Peripheral venous blood (5 ml) was collected from the proband, his parents and siblings, and the whole genome DNA was extracted.The proband's DNA was sequenced using whole exome sequencing.Hemizygous and potentially pathogenic mutations were verified by Sanger sequencing.Pathogenicity was assessed according to the American College of Medical Genetics and Genomics (ACMG) guidelines.Tools such as SpliceAI and dbscSNV were used to predict the impact of mutations on mRNA splicing.This study strictly followed the Declaration of Helsinki, and the study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2019[15]). All subjects and guardians of minor subjects signed informed consent forms.Results:The proband (Ⅲ: 1), a 5-year-old boy, presented with recessive nystagmus in both eyes and a best corrected visual acuity of 0.2.Color vision examination revealed red-green color blindness without night blindness.SD-OCT showed the presence of neuroepithelial structures in both eyes, but the interdigitation zone was blurred in both eyes.ff-ERG showed a slight decrease in rod function and a moderate-severe decrease in cone function in the right eye, and a slight decrease in cone and rod function in the left eye.Gene sequencing results showed that the proband had the hemizygous splice site variant c. 1911-3C>A of the CACNA1F gene on the X chromosome.Sanger sequencing showed that neither his mother nor his younger sister carried the variant, suggesting it was novel.This variant site was not recorded in the normal population database (PM2). Bioinformatics tools SpliceAI and dbscSNV consistently predicted that this variation affects on splicing.According to the ACMG guidelines, this variation is pathogenic. Conclusions:A novel variant c. 1911-3C>A in the CACNA1F gene was found in a family with CRD, and this variant may be a pathogenic variant site in this CRD family.This discovery expands the spectrum of pathogenic variations in CRD.
