A novel mutation of CNGB3 gene in a Chinese achromatopsia family

Authors: Zhou Zhongqiang,  Peng Haiying,  Shi Pingling,  Tang He,  Wei Yuanmeng,  Li Miao,  Lei Bo,  Huang Aiguo
DOI: 10.3760/cma.j.cn115989-20191217-00549
Published 2021-03-10
Cite as Chin J Exp Ophthalmol, 2021, 39(3): 221-227.

Abstract                                                     【Read Full Text】【Download PDF

Objective

To identify the pathogenic gene mutations in a Chinese achromatopsia family.

Methods

A pedigree investigation was performed.A Chinese Han pedigree from Luoyang city of China was enrolled in Henan Eye Hospital in November 2018.The medical history of the patients was collected.The best corrected visual acuity (BCVA) of the families was examined.The maniafestations of the anterior segment and fundus were obtained via slit lamp biomicroscope and slit lamp lens.The diopter was determined by objective and subjective refraction.Color vision was examined by Farnsworth-Munsell Hue Test.Retinal function was evaluated by international standard electroretinogram (ERG). Retina was observed by color photography, and its structural image was obtained by spectral-domain optical coherence tomography (SD-OCT). The peripheral blood sample was collected from the proband (Ⅲ1) and her younger brother (Ⅲ2) and parents for whole blood DNA extraction, and a whole genome sequencing (WGS) was performed to identify the pathogenic genes and mutation sites, and the sequencing data was compared through disease-related databases such as the Human Genome Databases due to a negative detective result of specific hereditary eye disease enrichment panel based on targeted exome capture technology.Sanger sequencing and bioinformatics analysis was carried out with softwares.The cosegregation analysis was performed.This study protocol was approved by an Ethics Committee of Henan Eye Hospital (No.HNEECKY-2019[15]) and complied with Declaration of Helsinki.Written informed consent was obtained from each subject or the guardian before any medical examination.

Results

This family included 2 patients and 8 members with normal phenotypes in 3 generations and showed an autosomal recessive inheritance model.Poor vision and photophobia appeared after birth in both Ⅲ1 and Ⅲ2, and these symptoms did not deteriorate with aging.Pigmentary mottling and atrophic changes could be seen in the retinas of the patients.Reflection bands of external membrane and ellipsoid line in macula of patients were irregular on the OCT image.Color vision examination showed achromatopsia of the patients.ERG indicated that the amplitudes of a-, b-waves of scotopic 0.01, 3.0, 10.0 ERG and oscillatory potentials were slightly reduced, and the amplitudes of a-, b-waves of photopic ERG and wavelets of 30 Hz were seriously reduced in both eyes of Ⅲ1 and Ⅲ2.WGS showed that heterozygous mutations of a novel mutation c. 129+ 1G>A and a known mutation c. 1285dupT of CNGB3 gene in Ⅲ1 and Ⅲ2.The mutations were confirmed by Sanger sequencing.

Conclusions

The compound heterozygous mutation in c. 129+ 1G>A/c.1285dupT of CNGB3 gene may be responsible for the achromatopsia pathogenesis in this Chinese Han pedigree.The abnormal phenotype of the patients is the result of both CNGB3 c. 129+ 1G>A and CNGB3 c. 1285dupT mutations simultaneously.

Key words:

Achromatopsia; Gene mutation; CNGB3 gene; Pedigree

Contributor Information

Zhou Zhongqiang
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
Shi Pingling
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
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
Lei Bo
Henan Eye Institute, Henan Eye Hospital, People’s Hospital of Zhengzhou University, Henan Provincial People’s Hospital, Zhengzhou 450003, China
Huang Aiguo
Henan Eye Institute, Henan Eye Hospital, People’s Hospital of Zhengzhou University, Henan Provincial People’s Hospital, Zhengzhou 450003, China
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Updated: March 16, 2021 — 7:49 am