AUTHOR=Fan Lihong , Ji Longfei , Xu Yuqing , Shen Guosong , Tang Kefeng , Li Zhi , Ye Sisi , Shen Xueping 

TITLE=A Novel Mutation c.3392G>T of COL2A1 Causes Spondyloepiphyseal Dysplasia Congenital by Affecting Pre-mRNA Splicing

JOURNAL=Frontiers in Genetics

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.827560

DOI=10.3389/fgene.2022.827560

ISSN=1664-8021

ABSTRACT=Spondyloepiphyseal dysplasia congenital (SEDC) is a rare chondrodysplasia caused by dominant pathogenic variants in collagen type II alpha 1 (COL2A1). Here, we detected a novel variant c.3392G>T of COL2A1 in a Chinese family with SEDC by targeted next-generation sequencing. Then the minigene analysis was carried out based on HeLa and HEK293T cell lines. Splicing assay indicates that the mutated minigene produces an alternatively spliced transcript with a skipping of exon 48, which generated an in-frame deletion of 15 amino acids (p. Gly1131_Pro1145del) in the COL2A1 protein. Due to the pathogenicity of the variation, we performed prenatal diagnosis on the proband’s wife, which indicated that the fetus carried the same mutation.