导致1B型肢带肌营养不良的典型剪接变异的体细胞和生发嵌合。

IF 1.9 3区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Guangyu Wang, Yaru Wang, Dandan Zhao, Chuanzhu Yan, Pengfei Lin
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引用次数: 0

摘要

1B型四肢带状肌营养不良症是由LMNA基因致病性变异引起的几种肌营养不良症之一。在这项研究中,我们调查了LGMD1B家族的临床、病理和遗传结果。基因测序发现,先证者和她的弟弟都携带LMNA基因的典型剪接c.513 + 1G > A变体。先证者的母亲没有该变异,先证者父亲的静脉血、尿液和精液样本中通过焦磷酸盐测序鉴定出一定比例的LMNA变异。进一步的cDNA分析表明,内含子2中的典型剪接c.513 + 1G > A变异诱导了内含子2前45 bp的保留,导致帧内插入15个氨基酸。我们的研究直接证实了LGMD1B家族中存在体细胞和生发嵌合现象,以及LMNA基因中典型剪接变异的致病性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Somatic and germinal mosaicism of a canonical splicing variant causing limb-girdle muscular dystrophy type 1B.

Limb-girdle muscular dystrophy type 1B is one of several muscular dystrophies caused by pathogenic variants in the LMNA gene. In this study, we investigated the clinical, pathological, and genetic findings of an LGMD1B family. Genetic sequencing identified the proband and her younger brother both carried the canonical splicing c.513 + 1G > A variant in the LMNA gene. The variant was absent in the proband's mother, and a certain percentage of the LMNA variant was identified in the venous blood, urine, and semen sample of the proband's father by pyrophosphate sequencing. Further cDNA analysis demonstrated that the canonical splicing c.513 + 1G > A variant in intron 2 induced retention of the first 45 bp of intron 2, resulting in an in-frame insertion of 15 amino acids. Our study directly confirmed the presence of somatic and germinal mosaicism in the LGMD1B family and the pathogenicity of the canonical splicing variant in the LMNA gene.

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来源期刊
Journal of Applied Genetics
Journal of Applied Genetics 生物-生物工程与应用微生物
CiteScore
4.30
自引率
4.20%
发文量
62
审稿时长
6-12 weeks
期刊介绍: The Journal of Applied Genetics is an international journal on genetics and genomics. It publishes peer-reviewed original papers, short communications (including case reports) and review articles focused on the research of applicative aspects of plant, human, animal and microbial genetics and genomics.
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