<i>DNAH6</i>is a novel candidate gene associated with sperm head anomaly

Li, L.; Sha, Yanwei; Xu, Xiaohui; Mei, Libin; Qiu, Pingping; Ji, Zhiyong; Lin, Shaobin; Su, Zhiying; Wang, C.; Yin, Chenghong; Li, P.

doi:10.1111/and.12953

Cited by 43 publications

(43 citation statements)

References 27 publications

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“…Previous studies have shown that dynein axonemal heavy chain 6 (DNAH6) is involved in generating the force required for ciliary beating, and mutations in this gene may cause primary ciliary dyskinesia, non-obstructive azoospermia, or sperm morphological defects [ 8 – 11 ]. By using a high-resolution array comparative genomic hybridization platform, a 171 kb deletion in DNAH6 was identified as the main etiology of POI in a patient [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

Whole-exome sequencing in patients with premature ovarian insufficiency: early detection and early intervention

et al. 2020

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Background The loss of ovarian function in women, referred to as premature ovarian insufficiency (POI), is associated with a series of concomitant diseases. POI is genetically heterogeneous, and in most cases, the etiology is unknown. Methods Whole-exome sequencing (WES) was performed on DNA samples obtained from patients with POI, and Sanger sequencing was used to validate the detected potentially pathogenic variants. An in silico analysis was carried out to predict the pathogenicity of the variants. Results We recruited 24 patients with POI and identified variants in POI-related genes in 14 patients, including bi-allelic mutations in DNAH6, HFM1, EIF2B2, BNC, and LRPPRC and heterozygous variants in BNC1, EIF2B4, FOXL2, MCM9, FANCA, ATM, EIF2B3, and GHR. No variants in the above genes were detected in the WES data obtained from 29 women in a control group without POI. Determining a clear genetic etiology could significantly increase patient compliance with appropriate intervention strategies. Conclusions Our study confirmed that POI is a genetically heterogeneous condition and that whole-exome sequencing is a powerful tool for determining its genetic etiology. The results of this study will aid researchers and clinicians in genetic counseling and suggests the potential of WES for the detection of POI and thus early interventions for patients with POI.

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Section: Discussionmentioning

confidence: 99%

Whole-exome sequencing in patients with premature ovarian insufficiency: early detection and early intervention

et al. 2020

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“…Other dynein proteins had been associated with spermatozoa function and morphology, including DNAH6 , DNAAF3 , and DNAL1 (Li et al., 2016, ; Mazor et al., ; Mitchison et al., ). Of these, mutations in DNAH6 and DNAAF3 have been noted in patients with spermatozoa characterized by abnormal flagella, reduced motility, and defective dynein.…”

Section: Discussionmentioning

confidence: 99%

DNAH17 is associated with asthenozoospermia and multiple morphological abnormalities of sperm flagella

Sha

Wei

Ding

et al. 2019

Annals of Human Genetics

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Background Multiple morphological abnormalities of the sperm flagella (MMAF) is one kind of severe asthenozoospermia, which is caused by dysplastic development of sperm flagella. In our study, we sought to investigate the novel gene mutations leading to severe asthenozoospermia and MMAF. Methods and Materials The patient's spermatozoa were tested by Papanicolaou staining and transmission electron microscopy. Whole exome sequencing was performed on the patient with severe asthenozoospermia and MMAF. Sanger sequencing verified the mutations in the family. The expression of DNAH17 was detected by immunofluorescence and Western blot. Results Spermatozoa sample from the patient showed severe asthenozoospermia and MMAF. We detected biallelic mutations (c.C4445T, p.A1482V and c.C6857T, and p.S2286L) in DNAH17 (MIM:610063). The protein expression of DNAH17 was almost undetectable in spermatozoa from the patient with the biallelic mutations. Conclusion These results demonstrated that DNAH17 may be involved in severe asthenozoospermia and MMAF.

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“…Mutations in several central pair complex and radial spoke head proteins have been identified in PCD patients. For patients with mutations in the C2 central pair projection gene HYDIN, infertility has been reported in affected men [59,91]. Subfertility caused by sperm motility defects have also been reported for male PCD patients with mutations in the radial spoke genes DNAJB13 (DnaJ heat shock protein family (Hsp40) member B13), RSPH3 (radial spoke head 3 homolog) and RSPH9 [13,27,37,48,62].…”

Section: The Effect Of Pcd Mutations In Dynein Arm Assembly Genes Andmentioning

confidence: 99%

Sperm defects in primary ciliary dyskinesia and related causes of male infertility

Sironen

Shoemark

Patel

et al. 2019

Cell. Mol. Life Sci.

178

134

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The core axoneme structure of both the motile cilium and sperm tail has the same ultrastructural 9 + 2 microtubular arrangement. Thus, it can be expected that genetic defects in motile cilia also have an effect on sperm tail formation. However, recent studies in human patients, animal models and model organisms have indicated that there are differences in components of specific structures within the cilia and sperm tail axonemes. Primary ciliary dyskinesia (PCD) is a genetic disease with symptoms caused by malfunction of motile cilia such as chronic nasal discharge, ear, nose and chest infections and pulmonary disease (bronchiectasis). Half of the patients also have situs inversus and in many cases male infertility has been reported. PCD genes have a role in motile cilia biogenesis, structure and function. To date mutations in over 40 genes have been identified cause PCD, but the exact effect of these mutations on spermatogenesis is poorly understood. Furthermore, mutations in several additional axonemal genes have recently been identified to cause a sperm-specific phenotype, termed multiple morphological abnormalities of the sperm flagella (MMAF). In this review, we discuss the association of PCD genes and other axonemal genes with male infertility, drawing particular attention to possible differences between their functions in motile cilia and sperm tails.

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DNAH6is a novel candidate gene associated with sperm head anomaly

Cited by 43 publications

References 27 publications

Whole-exome sequencing in patients with premature ovarian insufficiency: early detection and early intervention

Whole-exome sequencing in patients with premature ovarian insufficiency: early detection and early intervention

DNAH17 is associated with asthenozoospermia and multiple morphological abnormalities of sperm flagella

Sperm defects in primary ciliary dyskinesia and related causes of male infertility

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