Open AccessA Novel missense mutation of COL2A1 gene in a large family with stickler syndrome type I
Author(s) -
Liu Xiuzhen,
Dong Hongliang,
Gong Yuerong,
Wang Lianqing,
Zhang Ruyi,
Zheng Tihua,
Zheng Yuxi,
Shen Shuang,
Zheng Chelsea,
Tian Mingming,
Liu Naiguo,
Zhang Xiaolin,
Zheng Qing Yin
Publication year - 2022
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.17187
Subject(s) - missense mutation , genetics , phenotype , biology , exome sequencing , mutation , gene , minigene , exome , exon , alternative splicing
Stickler syndrome type I (STL1, MIM 108300) is characterized by ocular, auditory, skeletal and orofacial manifestations. Nonsyndromic ocular STL1 (MIM 609508) characterized by predominantly ocular features is a subgroup of STL1, and it is inherited in an autosomal dominant manner. In this study, a novel variant c.T100>C (p.Cys34Arg) in COL2A1 related to a large nonsyndromic ocular STL1 family was identified through Exome sequencing (ES). Bioinformatics analysis indicated that the variant site was highly conserved and the pathogenic mechanism of this variant may involve in affected structure of chordin‐like cysteine‐rich (CR) repeats of ColIIA. Minigene assay indicated that this variant did not change alternative splicing of exon2 of COL2A1 . Moreover, the nonsyndromic ocular STL1 family with 16 affected members showed phenotype variability and certain male gender trend. None of the family members had hearing loss. Our findings would expand the knowledge of the COL2A1 mutation spectrum, and phenotype variability associated with nonsyndromic ocular STL1. Search for genetic modifiers and related molecular pathways leading to the phenotype variation warrants further studies.