Related Experiment Video
Updated: Nov 16, 2025

Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models
Published on: December 9, 2016
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.
Purpose:
To identify the genetic factors responsible for asthenozoospermia, which is a major cause of male infertility characterized by immotile and malformed spermatozoa.
Methods:
Whole-exome sequencing was performed in two brothers from a family with asthenozoospermia to identify pathogenic variants. The functional effect of the identified variant was investigated in HEK293T cells using a minigene assay.
Results:
We identified a novel homozygous splicing variant c.6311-2A>G in DNAH8 from two affected brothers belonging to the same consanguineous family. The splicing variant altered a consensus splice acceptor site of DNAH8 intron 44, which led to the deletion of exon 45 and resulted in a frameshift and a predicted truncated protein (p.G2104Efs*19). Although most spermatozoa from the patients presented with reduced sperm motility, intracytoplasmic sperm injection was able to overcome the inability of the spermatozoa to reach the ovum and thus produce a healthy child for the proband.
Conclusions:
This finding expands the mutational spectrum of DNAH8, making it a potential genetic diagnostic marker for those suffering from primary male infertility.
Related Concept Videos
Alternative RNA Splicing
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
Alternative RNA Splicing
RNA Splicing
Exon Recombination
Exon shuffling follows “splice frame rules.” Each exon...
Nondisjunction
Nondisjunction

