Novel splicing variants in ARR3 gene cause the female- limited early-onset high myopia-Reference-Cited by-同舟云学术

Novel splicing variants in ARR3 gene cause the female- limited early-onset high myopia

Published:2023-07-12 Issue: Volume: Page:
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Author:

Niu Jianing¹,Zhu Weili²,Jin Xiaoying²,Teng Xiaoming¹,Zhang Junyu¹

Affiliation:

1. Tongji University

2. Jiaxing University

Abstract

Abstract X-linked heterozygous variants in ARR3 have been associated with the development of female-limited early-onset high myopia (eoHM). However, the clinical validity of this gene-disease association has yet to be systematically assessed. In this study, we identified two novel ARR3 splicing variants in two Chinese families affected by eoHM. Using minigene approach and RNA analyses, we found that both variants result in aberrant mRNA fragments, retaining a segment of the adjacent intron. The aberrant mRNA produced by c.39 + 1G > A variant and c.100 + 4A > G variant were both predicted to introduce a premature termination codon, resulting in a truncated protein. Additionally, we curated the clinical validity of ARR3 and eoHM as as "Definitive" using the ClinGen Gene Curation Framework. Thus, our study not only demonstrated that two novel ARR3 splicing variants are associated with eoHM but also confirmed the clinical validity of ARR3 and eoHM.

Publisher

Research Square Platform LLC

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