Fan Lihong, Ji Longfei, Xu Yuqing, Shen Guosong, Tang Kefeng, Li Zhi, Ye Sisi, Shen Xueping
Center of Prenatal Diagnosis, Huzhou Maternity & Child Health Care Hospital, Huzhou, China.
Department of Clinical Laboratory, The First People's Hospital of Huzhou, Huzhou, China.
Front Genet. 2022 Apr 5;13:827560. doi: 10.3389/fgene.2022.827560. eCollection 2022.
Spondyloepiphyseal dysplasia congenital (SEDC) is a rare chondrodysplasia caused by dominant pathogenic variants in . Here, we detected a novel variant c.3392G > T (NM_001844.4) of in a Chinese family with SEDC by targeted next-generation sequencing. To confirm the pathogenicity of the variant, we generated an appropriate minigene construct based on HeLa and HEK293T cell lines. Splicing assay indicated that the mutated minigene led to aberrant splicing of pre-mRNA and produced an alternatively spliced transcript with a skipping of partial exon 48, which generated a predicted 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.
先天性脊椎骨骺发育不良（SEDC）是一种由……中的显性致病变异引起的罕见软骨发育不良。在此，我们通过靶向二代测序在中国一个患有SEDC的家族中检测到了一个新的……变体c.3392G>T（NM_001844.4）。为了证实该变体的致病性，我们基于HeLa和HEK293T细胞系构建了合适的小基因载体。剪接分析表明，突变的小基因导致……前体mRNA的异常剪接，并产生了一个选择性剪接的转录本，该转录本缺失了部分第48外显子，这导致了胶原蛋白2A1（COL2A1）蛋白中预测的15个氨基酸的框内缺失（p.Gly1131_Pro1145del）。由于该变异具有致病性，我们对先证者的妻子进行了产前诊断，结果表明胎儿携带相同的突变。
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