Novel compound heterozygous variants in the USH2A gene associated with autosomal recessive retinitis pigmentosa without hearing loss

Yanxia Huang; Lamei Yuan; Guiyun He; Yanna Cao; Xiong Deng; Hao Deng

doi:10.3389/fcell.2023.1129862

Novel compound heterozygous variants in the USH2A gene associated with autosomal recessive retinitis pigmentosa without hearing loss

Front Cell Dev Biol. 2023 Feb 15:11:1129862. doi: 10.3389/fcell.2023.1129862. eCollection 2023.

Authors

Yanxia Huang^{1

2

3}, Lamei Yuan^{1

2

3}, Guiyun He⁴, Yanna Cao⁵, Xiong Deng^{1

2

3}, Hao Deng^{1

2

3

6}

Affiliations

¹ Health Management Center, The Third Xiangya Hospital, Central South University, Changsha, China.
² Center for Experimental Medicine, The Third Xiangya Hospital, Central South University, Changsha, China.
³ Disease Genome Research Center, Central South University, Changsha, China.
⁴ Department of Ophthalmology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China.
⁵ Department of Ophthalmology, The Third Xiangya Hospital, Central South University, Changsha, China.
⁶ Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, China.

Abstract

Background: Retinitis pigmentosa (RP) is a group of progressive inherited retinal dystrophies characterized by the primary degeneration of rod photoreceptors and the subsequent loss of cone photoreceptors because of cell death. It is caused by different mechanisms, including inflammation, apoptosis, necroptosis, pyroptosis, and autophagy. Variants in the usherin gene (USH2A) have been reported in autosomal recessive RP with or without hearing loss. In the present study, we aimed to identify causative variants in a Han-Chinese pedigree with autosomal recessive RP. Methods: A six-member, three-generation Han-Chinese family with autosomal recessive RP was recruited. A full clinical examination, whole exome sequencing, and Sanger sequencing, as well as co-segregation analysis were performed. Results: Three heterozygous variants in the USH2A gene, c.3304C>T (p.Q1102*), c.4745T>C (p.L1582P), and c.14740G>A (p.E4914K), were identified in the proband, which were inherited from parents and transmitted to the daughters. Bioinformatics analysis supported the pathogenicity of the c.3304C>T (p.Q1102*) and c.4745T>C (p.L1582P) variants. Conclusions: Novel compound heterozygous variants in the USH2A gene, c.3304C>T (p.Q1102*) and c.4745T>C (p.L1582P), were identified as the genetic causes of autosomal recessive RP. The findings may enhance the current knowledge of the pathogenesis of USH2A-associated phenotypes, expand the spectrum of the USH2A gene variants, and contribute to improved genetic counseling, prenatal diagnosis, and disease management.

Keywords: compound heterozygous variants; photoreceptor cell death; retinitis pigmentosa; usherin gene; whole exome sequencing.

Grants and funding

This work was funded by National Natural Science Foundation of China (81873686 and 81800219), Natural Science Foundation of Hunan Province (2020JJ3057 and 2020JJ4830), Scientific Research Project of Health Commission of Hunan Province (A202303018385), Distinguished Professor of the Lotus Scholars Award Program of Hunan Province, Wisdom Accumulation and Talent Cultivation Project of the Third Xiangya Hospital of Central South University (YX202109), and Fundamental Research Funds for the Central Universities of Central South University (2021zzts218).