Novel compound heterozygous variants in dynein axonemal heavy chain 17 cause asthenoteratospermia with sperm flagellar defects

Song, Bing; Liu, Chunyu; Gao, Yang; Marley, Jordan Lee; Li, Weiyu; Ni, Xiaoqin; Liu, Wangjie; Chen, Yujie; Wang, Jiajia; Wang, Chao; Zhou, Ping; Wei, Zhaolian; He, Xiaojin; Zhang, Feng; Cao, Yunxia

doi:10.1016/j.jgg.2020.07.004

Cited by 8 publications

(7 citation statements)

References 19 publications

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“…The outer dense fibers' structure was also disrupted. Even though the concentrations of the sperm samples were normal, there were various defects in the sperm tails—some of them were missing, others were shorter than normal, coiled, or presented with uneven caliber 52 …”

Section: Resultsmentioning

confidence: 98%

“…Even though the concentrations of the sperm samples were normal, there were various defects in the sperm tails-some of them were missing, others were shorter than normal, coiled, or presented with uneven caliber. 52 In their most recent study, Zheng et al looked at a male patient who was infertile and had a low sperm count and MMAF. The patient was a homozygous carrier of a variant in the DNAH17 gene.…”

Section: Dnah17mentioning

confidence: 99%

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Potential role of dynein‐related genes in the etiology of male infertility: A systematic review and a meta‐analysis

2022

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Background The dynein‐related genes may have a role in the etiology of male infertility, particularly in cases of impaired sperm motility. Objectives The goal of this review is to compile a list of the most important dynein‐related candidate genes that may contribute to male factor infertility. Materials and methods Databases were searched using the keywords “dynein,” “male,” “infertility,” and by applying strict inclusion criteria. A meta‐analysis was also performed by using the eligible case‐control studies. The odd ratios (ORs), the Z‐test score, and the level of significance were determined using a fixed model with a p value of 0.05. Funnel plots were used to check for publication bias. Results There were 35 studies that met the inclusion criteria. There were a total of 15 genes responsible for the production of dynein structural proteins, the production of dynein assembling factors, and potentially associated with male infertility. A total of five case‐control studies were eligible for inclusion in the meta‐analysis. Variants in the dynein‐related genes were linked to an increased the risk of male infertility (OR = 21.52, 95% confidence interval 8.34–55.50, Z test = 6.35, p < 0.05). The percentage of heterogeneity, I2, was 47.00%. The lack of variants in the dynein genes was an advantage, and this was statistically significant. Discussion The results from the present review illustrate that pathogenic variants in genes both for dynein synthesis and for dynein assembly factors could be associated with isolated cases of male infertility without any other symptoms. Conclusions The genes addressed in this study, which are involved in both the production and assembly of dynein, could be used as molecular targets for future research into the etiology of sperm motility problems.

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Section: Resultsmentioning

confidence: 98%

Section: Dnah17mentioning

confidence: 99%

Potential role of dynein‐related genes in the etiology of male infertility: A systematic review and a meta‐analysis

2022

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“…Interestingly, similar differences in sperm phenotype were also reported for other asthenoteratozoospermia-related genes, such as DNAH10 (MIM: 605884), CFAP47, DNAH8 (MIM: 603337), TTC29 (MIM: 618735), and DNAH17 (MIM: 610063). 16,39,40,41,42 The cause of variable sperm concentration and motility may be partially related to variation types and variation sites, individual heterogeneity, phenotypic heterogeneity, and/ or differences in environment and lifestyle among males with the DNHD1 variation.…”

Section: Discussionmentioning

confidence: 99%

Bi-allelic variants in DNHD1 cause flagellar axoneme defects and asthenoteratozoospermia in humans and mice

Tan

Meng

et al. 2022

The American Journal of Human Genetics

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“…DNAH8 has been identified in three MMAF cohorts, and it encodes a γ-type heavy-chain protein, which is an ODA component ( Liu et al, 2020b ; Yang et al, 2020 ; Weng et al, 2021 ). Another ODA component, β-type heavy chain, which is encoded by the DNAH17 gene, acts as a MMAF causative gene ( Whitfield et al, 2019 ; Sha et al, 2020a ; Song et al, 2020 ; Zhang et al, 2020 ; Zhang G. et al, 2021 ; Zhang B. et al, 2021 ; Zheng et al, 2021 ; Liu G. et al, 2022 ). Moreover, DNAH8 or DNAH17 is absent when the other is deficient, and they are co-localized along the axoneme, indicating interaction between these two proteins ( Whitfield et al, 2019 ; Liu et al, 2020a ).…”

Section: Pathogenic Genes and Their Function Inspermatogenesismentioning

confidence: 99%

Clinical detection, diagnosis and treatment of morphological abnormalities of sperm flagella: A review of literature

Wang

Zheng

et al. 2022

Front. Genet.

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Sperm carries male genetic information, and flagella help move the sperm to reach oocytes. When the ultrastructure of the flagella is abnormal, the sperm is unable to reach the oocyte and achieve insemination. Multiple morphological abnormalities of sperm flagella (MMAF) is a relatively rare idiopathic condition that is mainly characterized by multiple defects in sperm flagella. In the last decade, with the development of high-throughput DNA sequencing approaches, many genes have been revealed to be related to MMAF. However, the differences in sperm phenotypes and reproductive outcomes in many cases are attributed to different pathogenic genes or different pathogenic mutations in the same gene. Here, we will review information about the various phenotypes resulting from different pathogenic genes, including sperm ultrastructure and encoding proteins with their location and functions as well as assisted reproductive technology (ART) outcomes. We will share our clinical detection and diagnosis experience to provide additional clinical views and broaden the understanding of this disease.

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Novel compound heterozygous variants in dynein axonemal heavy chain 17 cause asthenoteratospermia with sperm flagellar defects

Cited by 8 publications

References 19 publications

Potential role of dynein‐related genes in the etiology of male infertility: A systematic review and a meta‐analysis

Potential role of dynein‐related genes in the etiology of male infertility: A systematic review and a meta‐analysis

Bi-allelic variants in DNHD1 cause flagellar axoneme defects and asthenoteratozoospermia in humans and mice

Clinical detection, diagnosis and treatment of morphological abnormalities of sperm flagella: A review of literature

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