Open AccessIntron retention by a novel intronic mutation in DKC1 gene caused recurrent still birth and early death in a Chinese family
Author(s) -
Guo Qiufang,
Zhang Ping,
Ying Wenjing,
Wang Yaqiong,
Zhu Jitao,
Li Gang,
Wang Huijun,
Wang Xiaochuan,
Lei Caixia,
Zhou Wenhao,
Sun Jinqiao,
Wu Bingbing
Publication year - 2022
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1934
Subject(s) - minigene , dyskeratosis congenita , biology , genetics , telomerase , mutation , frameshift mutation , intron , proband , sanger sequencing , rna splicing , gene , rna
Background DKC1 , the dyskerin encoding gene, functions in telomerase activity and telomere maintenance. DKC1 mutations cause a multisystem disease, dyskeratosis congenita (DC), which is associated with immunodeficiency and bone marrow failure. Methods In this research, we reported a novel intronic mutation of DKC1 causing dyskerin functional loss in a Chinese family. Whole exome sequence (WES) of the proband and validation by sanger sequencing help us identify a pathogenic DKC1 mutation. Minigene splicing assays were performed to evaluate functional change of DKC1 . Results A pathogenic DKC1 intronic mutation(c.84 + 7A > G) was identified in the proband, which was inherited from heterozygous mother and not reported before. We detected the novel transcript with a 7 bp intron retention through minigene splicing assay. The newly spliced transcript is so short that would be degraded by nonsense‐mediated mRNA decay in vitro and we infer that the novel DKC1 mutation would influences normal physiological function of dyskerin. Conclusions Our study identified a novel intronic mutation, which expands the spectrum of pathogenic DKC1 gene mutations and can be used in molecular diagnosis. The mutant allele was transmitted to the next generation with high frequency in the family and causes still birth or early death.