Analysis of genotype and phenotype of hereditary retinal diseases which are easily misdiagnosed as amblyopia

Authors: Qi Rui,  Zhu Jinyan,  Wang Xiaoguang,  Zhuang Wenjuan,  Sheng Xunlun

DOI: 10.3760/cma.j.issn.2095-0160.2019.11.008
Published 2019-11-10
Cite as Chin J Exp Ophthalmol, 2019,37(11): 888-895.

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To analysis the genotype and phenotype of hereditary retinal diseases (HRD) which are easily misdiagnosed as amblyopia.


A case-control study was designed.The patients with HRD who were misdiagnosed as amblyopia in Ningxia Eye Hospital from January to December, 2017 were recruited in this study.The clinical medical history and ophthalmic examinations of patients and their family members were recorded, and family maps were drawed.Peripheral venous blood (5 ml) from each patient and their family members was collected, and genomic DNA was extract.The target sequence capture sequencing technology was used to detect the genetic testing in serum of the patient, and the pathogenic mutation site was determined by Sanger sequencing and co-segregation verification.Genetic testing results with related ophthalmic examination were considered together to analyze the relationship between genotype and phenotype.This study followed the Declaration of Helsinki.Written informed consent was obtained from each subject or the guardian prior to entering study cohort.This study protocol was approved by Ethic Committee of People’s Hospital of Ningxia Hui Autonomous Region Hospital (No.2016018).


Twenty-two patients with HRD were enrolled in the study, including 10 Stargardt disease (STGD), 8 cases of cone dystrophy (COD) or cone and rod dystrophy (CRD), and 5 cases of familial exudative vitreoretinopathy(FEVER). Nine patients were detected to have pathogenic mutations, and the positive rate was 40.9%, of which 4 patients with STGD carried mutation gene, including ABCA4 and PROM1 genes; mutations in RPGRPROM1 and GUCY2D genes were detected in 3 patients with COD or CRD; TSPAN12 gene mutation were detected in 2 patients with FEVER.Eleven mutation sites were detected, 4 of which were newly discovered mutation sites.All of the patients in 9 HRD families developed symptoms during adolescence.At the early stage of the disease, there was severe damage to the eyesight, but the fundus was normal or only slightly abnormal.As the disease progressed, the fundus changes were characteristic, and there were clinical phenotypic overlap between some diseases.All family genotypes and clinical phenotypes were co-separated.


The main pathogenic gene of STGD is ABCA4 gene, and PROM1 gene can also cause partial STGD; COD and CRD have similar clinical manifestations, and the pathogenic genes also cross each other, and the genetic pattern is diverse; FEVER caused by mutation of TSPAN12 gene is autosomal dominant, and the mutation type has missense mutation and frameshift mutation.HRDs lack typical early clinical signs, and genetic diagnosis can provide pre-symptomatic diagnosis.

Key words:

Hereditary retinal disease; Genotype; Phenotype

Contributor Information

Qi Rui
Department of Ophthalmology, Ningxia Eye Hospital, People’s Hospital of Ningxia Hui Autonomous Region, First Affiliated Hospital of Northwest University for Nationalities, Ningxia Clinical Research Center on Diseases of Blindness in Eye, Yinchuan 750002, China
Zhu Jinyan
Wang Xiaoguang
Zhuang Wenjuan
Sheng Xunlun
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Updated: December 28, 2022 — 1:37 am