Bi-allelic Loss-of-function Variants in CFAP58 Cause Flagellar Axoneme and Mitochondrial Sheath Defects and Asthenoteratozoospermia in Humans and Mice

He, Xiaojin; Liu, Chunyu; Yang, Xiaoyu; Lv, Mingrong; Ni, Xiaoqing; Li, Qiang; Cheng, Hongju; Liu, Wangjie; Tian, Shixiong; Wu, Huan; Gao, Yang; Yang, Clayton S.-C.; Tan, Qing; Cong, Jiangshan; Tang, Dongdong; Zhang, Jingjing; Song, Bing; Zhong, Yading; Li, Hang; Zhi, Weiwei; Mao, Xiaohong; Fu, Feifei; Ge, Liang; Shen, Qunshan; Zhang, Manyu; Saiyin, Hexige; Li, Jin; Xu, Yuping; Zhou, Ping; Wei, Zhaolian; Zhang, Feng; Cao, Yunxia

doi:10.1016/j.ajhg.2020.07.010

Cited by 92 publications

(62 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…No obvious lung abnormalities were detected in the chest X‐ray images of the two patients. He et al reported that their subjects presented no apparent PCD‐related symptoms 5 . This phenomenon may be due to CFAP58 being highly specifically expressed in the human testis and flagella and thus having little effect on the human cilia.…”

Section: Discussionmentioning

confidence: 91%

“…Considering that CFAP58 is highly expressed in the testis, especially in the sperm flagella, 4 it is suspected that CFAP58 plays an essential role in the development of the sperm flagellum. Recent studies have shown that biallelic variants of CFAP58 could cause defects in the flagellar axoneme and mitochondrial sheath (MS) of sperm that eventually result in the development of the asthenoteratozoospermia phenotype in humans and mice 5 …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Biallelic mutations of CFAP58 are associated with multiple morphological abnormalities of the sperm flagella

Sha¹,

Sha

Liu

et al. 2020

Clinical Genetics

View full text Add to dashboard Cite

Multiple morphological abnormalities of the sperm flagella (MMAF) is a severe type of teratozoospermia. In this study, whole‐exome sequencing was conducted on 55 patients with MMAF, and biallelic mutations of CFAP58 were identified in two patients. The variants are rare and pathogenic, and CFAP58 was absent in the CFAP58‐mutated sperm. The F037/II:1 couple benefited from intracytoplasmic sperm injection (ICSI). This study further indicated that CFAP58 is a pathogenic gene associated with MMAF and ICSI is an effective treatment.

show abstract

Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Biallelic mutations of CFAP58 are associated with multiple morphological abnormalities of the sperm flagella

Sha¹,

Sha

Liu

et al. 2020

Clinical Genetics

View full text Add to dashboard Cite

show abstract

“…Multiple morphological abnormalities of the sperm flagella (MMAF) is a severe form of asthenoteratozoospermia. Variants of several genes, including CFAP family members ( CFAP43 , CFAP44 [ 132 , 133 ], CFAP58 [ 134 ], CFAP69 [ 135 ], and CFAP251 [ 136 ]), DNAH8 [ 137 ], ARMC2 [ 138 ], TTC21A [ 139 ], and QRICH2 [ 140 ], lead to multiple morphological abnormalities of the sperm flagella and primary male infertility. Mutation in PMFBP1 [ 141 ] is involved in asthenospermia syndrome.…”

Section: Novel Gene Regulation In Abnormal Human Spermatogenesismentioning

confidence: 99%

Novel Gene Regulation in Normal and Abnormal Spermatogenesis

Chen

Cheng

et al. 2021

Cells

View full text Add to dashboard Cite

Spermatogenesis is a complex and dynamic processwhich is precisely controlledby genetic and epigenetic factors. With the development of new technologies (e.g., single-cell RNA sequencing), increasingly more regulatory genes related to spermatogenesis have been identified. In this review, we address the roles and mechanisms of novel genes in regulatingthenormal and abnormal spermatogenesis. Specifically, we discussed the functions and signaling pathways of key new genes in mediating the proliferation, differentiation, and apoptosis of rodent and human spermatogonial stem cells (SSCs), as well as in controlling the meiosis of spermatocytes and other germ cells. Additionally, we summarized the gene regulation in the abnormal testicular microenvironment or the niche by Sertoli cells, peritubularmyoid cells, and Leydig cells. Finally, we pointed out the future directions for investigating the molecular mechanisms underlying human spermatogenesis. This review could offer novel insights into genetic regulation in the normal and abnormal spermatogenesis, and it provides new molecular targets for gene therapy of male infertility.

show abstract

“…The cilia and flagella associated protein (CFAP) family, such as CFAP58, CFAP61, CFAP69, CFAP65, CFAP43, CFAP44, CFAP70 , and CFAP251 , is associated with flagellum biogenesis and morphogenesis (Beurois et al, 2019; Dong FN, 2018; He et al, 2020; Huang et al, 2020; W. Li et al, 2019; Li et al, 2020; Tang et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Essential role of CFAP53 in sperm flagellum biogenesis

Liu

et al. 2021

Preprint

View full text Add to dashboard Cite

The sperm flagellum is essential for male fertility. Despite vigorous research progress towards understanding the pathogenesis of flagellum-related diseases, much remains unknown about the mechanisms underlying the flagellum biogenesis itself. Here, we show that the cilia and flagella associated protein 53 (Cfap53) gene is predominantly expressed in testes, and it is essential for sperm flagellum biogenesis. The knockout of this gene resulted in complete infertility in male mice but not in the females. CFAP53 localized to the manchette and sperm tail during spermiogenesis, the knockout of this gene impaired flagellum biogenesis. Furthermore, we identified two manchette and sperm tail-associated proteins that interacted with CFAP53 during spermiogenesis. The disruption of Cfap53 decreased the expression level of these two proteins and disrupted their localization in spermatids. Together, our results suggest that CFAP53 is an essential protein for sperm flagellum biogenesis, and its mutations might be associated with MMAF.

show abstract

Bi-allelic Loss-of-function Variants in CFAP58 Cause Flagellar Axoneme and Mitochondrial Sheath Defects and Asthenoteratozoospermia in Humans and Mice

Cited by 92 publications

References 42 publications

Biallelic mutations of CFAP58 are associated with multiple morphological abnormalities of the sperm flagella

Biallelic mutations of CFAP58 are associated with multiple morphological abnormalities of the sperm flagella

Novel Gene Regulation in Normal and Abnormal Spermatogenesis

Essential role of CFAP53 in sperm flagellum biogenesis

Contact Info

Product

Resources

About