线粒体 DNA 插入 CD40 配体基因相关的 X 连锁高免疫球蛋白 M 综合征。
Mitochondrial DNA insert into CD40 ligand gene-associated X-linked hyper-IgM syndrome.
机构信息
Department of Pulmonology, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.
出版信息
Mol Genet Genomic Med. 2021 May;9(5):e1646. doi: 10.1002/mgg3.1646. Epub 2021 Mar 24.
BACKGROUND
X-linked hyper-IgM (X-HIGM), which results from mutations in the CD40LG gene located on chromosome Xq26.3, is the most common form of HIGM. To date, more than 130 variants of the CD40L gene have been reported. We described a patient with novel de novo nuclear mitochondrial DNA sequences (NUMTs) in the CD40LG gene that have resulted in X-HIGM.
METHODS
Whole-exome sequencing (WES) analysis was used to screen for causal variants in the genome, and the candidate breakpoint was confirmed by Sanger sequencing.
RESULTS
A new mutation of CD40LG, which deletes A at position 17 followed by a 147-nucleotide from mitochondrial DNA copies insertion in exon 1, was detected in a 20-month-old boy harbouring an X-HIGM combined with immunodeficiency syndrome.
CONCLUSION
This is one of the few cases of a human genetic disease caused by nuclear mitochondrial DNA sequences (NUMTs). The presented data serve to demonstrate that de novo NUMT transfer of nucleic acid is a novel mechanism of X-HIGM.
背景
X 连锁高免疫球蛋白 M 血症（X-HIGM）是由于位于 Xq26.3 染色体上的 CD40LG 基因发生突变引起的，是最常见的 HIGM 形式。迄今为止，已经报道了超过 130 种 CD40L 基因突变。我们描述了一名患者，其 CD40LG 基因中存在新的从头核线粒体 DNA 序列（NUMTs），导致 X-HIGM。
方法
全外显子组测序（WES）分析用于筛选基因组中的因果变异，候选断点通过 Sanger 测序确认。
结果
在一名患有 X-HIGM 合并免疫缺陷综合征的 20 个月大男孩中，检测到 CD40LG 的新突变，该突变为 1 号外显子中 A17 缺失，随后插入 147 个核苷酸的线粒体 DNA 拷贝。
结论
这是少数由核线粒体 DNA 序列（NUMTs）引起的人类遗传疾病之一。所提供的数据表明，核线粒体 DNA 序列的从头转移是 X-HIGM 的一种新机制。
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