Genotype and clinical phenotype analysis of a five-generation Ningxia family with autosomal dominant retinitis pigmentosa pedigree

Authors: Rong Weining,  Zhang Fangxia,  Liu Yani,  Lei Bo,  Sheng Xunlun

DOI: 10.3760/cma.j.cn115989-20190212-00050
Published 2020-08-10
Cite as Chin J Exp Ophthalmol, 2020,38(08): 675-679.

Abstract                              [View PDF] [Read Full Text]

Objective

To identify the pathogenic mutation in a five-generation Ningxia family with autosomal dominant retinitis pigmentsoa (adRP) and to analyze its associated clinical phenotype.

Methods

One adRP pedigree was recruited for this study.All the patients and family members received complete ophthalmic examinations.DNA was abstracted from peripheral blood of three patients, one normal family member and 300 normal controls.Using whole exome sequencing (WES) chip and bioinformatics analysis to screen the candidate disease-causing mutations.PCR and direct sequencing were used to confirm the disease-causing mutations.Genotype-phenotype correlation was also analyzed.This study followed the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of People’s Hospital of Ningxia Hui Autonomous Region (No.20160204).

Results

PRPF31 c. C1048T (p.Q350X) nonsense mutation was identified as the disease-causing mutation for this family by WES chip, PCR and direct sequencing.This family demonstrated early onset of the disease by presenting nyctalopia from 5 to 6 years, performed rapid disease progression, severely impaired visual function and posterior subcapsular cataract.The fundus presentations and electroretinogram (ERG) results showed typical RP progressions.

Conclusions

PRPF31 c. C1048T (p.Q350X) nonsense mutation is the disease-causing mutation of this family.This mutation is first reported in Chinese with distinct phenotypes in the present family, including early onset of the disease, rapid disease progression, severely impaired visual function and posterior subcapsular cataract.

Key words:

Autosomal dominant retinitis pigmentosa; Genotype; Phenotype

Contributor Information

Rong Weining
Ningxia Eye Hospital, People’s Hospital of Ningxia Hui Automous Region, First Affiliated Hospital of Northwest University for Nationalities, Ningxia Clinical Research Center on Diseases of Blindness in Eye, Ningxia 750001, China
Zhang Fangxia
Ningxia Eye Hospital, People’s Hospital of Ningxia Hui Automous Region, First Affiliated Hospital of Northwest University for Nationalities, Ningxia Clinical Research Center on Diseases of Blindness in Eye, Ningxia 750001, China
Liu Yani
Ningxia Eye Hospital, People’s Hospital of Ningxia Hui Automous Region, First Affiliated Hospital of Northwest University for Nationalities, Ningxia Clinical Research Center on Diseases of Blindness in Eye, Ningxia 750001, China
Lei Bo
Ningxia Eye Hospital, People’s Hospital of Ningxia Hui Automous Region, First Affiliated Hospital of Northwest University for Nationalities, Ningxia Clinical Research Center on Diseases of Blindness in Eye, Ningxia 750001, China
Sheng Xunlun
Ningxia Eye Hospital, People’s Hospital of Ningxia Hui Automous Region, First Affiliated Hospital of Northwest University for Nationalities, Ningxia Clinical Research Center on Diseases of Blindness in Eye, Ningxia 750001, China
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