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A novel splicing variant in DNAH8 causes asthenozoospermia
Zhou Zhou1, Xiaoyan Mao2, Biaobang Chen3
1Institute of Pediatrics, Children's Hospital of Fudan University, the Institutes of Biomedical Sciences, and the State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, 200032, China.
Journal of Assisted Reproduction and Genetics
|February 21, 2021
Summary
A novel DNAH8 gene variant causes asthenozoospermia, a male infertility condition. This discovery offers a potential genetic diagnostic marker for primary male infertility.
Area of Science:
- Genetics
- Reproductive Medicine
- Molecular Biology
Background:
- Asthenozoospermia, characterized by immotile and malformed spermatozoa, is a significant cause of male infertility.
- Identifying the genetic underpinnings of asthenozoospermia is crucial for diagnosis and potential therapeutic strategies.
Purpose of the Study:
- To identify the genetic factors responsible for asthenozoospermia in a consanguineous family.
- To characterize a novel genetic variant associated with male infertility.
Main Methods:
- Whole-exome sequencing was employed to identify pathogenic variants in two affected brothers.
- Functional analysis of the identified variant was conducted using a minigene assay in HEK293T cells.
Main Results:
- A novel homozygous splicing variant (c.6311-2A>G) in the DNAH8 gene was identified in the affected individuals.
- This variant disrupted the splice acceptor site, leading to exon deletion, frameshift, and a predicted truncated DNAH8 protein.
- Despite reduced sperm motility, intracytoplasmic sperm injection enabled successful conception and the birth of a healthy child.
Conclusions:
- The identified DNAH8 variant expands the known spectrum of mutations causing asthenozoospermia.
- DNAH8 is implicated as a potential genetic cause of primary male infertility.
- This finding highlights DNAH8 as a candidate for genetic diagnostic testing in infertile males.
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