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Mitochondrial DNA insert into CD40 ligand gene-associated X-linked hyper-IgM syndrome
Xuejing Li1, Dan Xu1, Beilei Cheng1
1Department of Pulmonology, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.
Insights
A novel genetic mutation causing X-linked hyper-IgM (X-HIGM) was identified. This rare condition resulted from nuclear mitochondrial DNA sequences (NUMTs) inserting into the CD40LG gene, offering a new understanding of X-HIGM.
Area of Science:
- Genetics
- Immunology
- Molecular Biology
Background:
- X-linked hyper-IgM (X-HIGM) is the most common form of hyper-IgM, typically caused by mutations in the CD40LG gene.
- Over 130 variants of the CD40L gene have been reported, leading to various genetic disorders.
- This study focuses on a unique case involving novel genetic alterations.
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.
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