ArticleAmerican journal of human genetics2019
Bi-allelic Mutations in TTC21A Induce Asthenoteratospermia in Humans and Mice.
Open access · bronzeAbstract read
In one paragraph
Article in American journal of human genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed
14.5field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
70 citing papers in PubMed, 134 citations in OpenAlex.
- Novel IFT140 variants cause spermatogenic dysfunction in humans.Molecular genetics & genomic medicine · 2019Trial
- CFAP58-deficient human sperm show radial spoke-doublet microtubule interface abnormalities and successful fertilization by ICSI.Journal of assisted reproduction and genetics · 2026Article
- Genome-Wide Analysis of DNA Methylation Profiles on Jining Grey Goat Uterus Associated with Prolificacy Using Whole-Genome Bisulfite Sequencing.Animals : an open access journal from MDPI · 2026Article
- Novel mutations in FSIP2 cause male infertility through multiple morphological abnormalities of the sperm flagella.Asian journal of andrology · 2026Article
- A novel frameshift variant inFrontiers in cell and developmental biology · 2026Article
- The intricate dance of RNA-binding proteins: unveiling the mechanisms behind male infertility.Human reproduction update · 2026Review
- Mutations in CFAP57 disrupt the localization of MYH10 and IFT88, leading to flagellogenesis failure in humans and mice.Human genomics · 2025Article
- CFAP300 loss-of-function variant causes primary ciliary dyskinesia and male infertility via disrupting sperm flagellar assembly and acrosome formation.Asian journal of andrology · 2025Article
- Human asthenozoospermia: Update on genetic causes, patient management, and clinical strategies.Andrology · 2025Review
- Function of manchette and intra-manchette transport in spermatogenesis and male fertility.Cell communication and signaling : CCS · 2025Review
- Homozygous deleterious variants in MYCBPAP induce asthenoteratozoospermia involving abnormal acrosome biogenesis, manchette structure and sperm tail assembly in humans and mice.Science China. Life sciences · 2025Article
- A novel homozygous splicing mutation in AK7 causes multiple morphological abnormalities of sperm flagella in patients from consanguineous Pakistani families.Asian journal of andrology · 2025Article
- Novel homozygous SPAG17 variants cause human male infertility through multiple morphological abnormalities of spermatozoal flagella related to axonemal microtubule doublets.Asian journal of andrology · 2025Article
- A Systematic Review of Mendelian Randomization in Spontaneous Miscarriage.Journal of multidisciplinary healthcare · 2025Review
- Mapping the proteome landscape of Indian Zebu (Sahiwal) spermatozoa using high-resolution mass spectrometry andAnimal biotechnology · 2024Article
- Genetic etiological spectrum of sperm morphological abnormalities.Journal of assisted reproduction and genetics · 2024Review
- Whole exome sequencing analysis of 167 men with primary infertility.BMC medical genomics · 2024Article
- Conserved genes regulating human sex differentiation, gametogenesis and fertilization.Journal of translational medicine · 2024Review
- Review
- Identification of novel homozygous asthenoteratospermia-causing ARMC2 mutations associated with multiple morphological abnormalities of the sperm flagella.Journal of assisted reproduction and genetics · 2024Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
26 authors at 4 institutions in 2 countries.
Wangjie LiuObstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai 200011, China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China; State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211116, China.
Xiaojin HeReproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, Hefei 230022, China; Anhui Provincial Engineering Technology Research Center for Biopreservation and Artificial Organs, Hefei 230022, China.
Shenmin YangState Key Laboratory of Reproductive Medicine, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215002, China; Suzhou Municipal Hospital, Suzhou 215002, China.
Raoudha ZouariPolyclinique les Jasmins, Centre d'Aide Médicale à la Procréation, Centre Urbain Nord, 1003 Tunis, Tunisia.
Jiaxiong WangState Key Laboratory of Reproductive Medicine, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215002, China; Suzhou Municipal Hospital, Suzhou 215002, China.
Huan WuReproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, Hefei 230022, China; Anhui Provincial Engineering Technology Research Center for Biopreservation and Artificial Organs, Hefei 230022, China.
Zine-Eddine KherrafGenetic Epigenetic and Therapies of Infertility, Institute for Advanced Biosciences, Institut National de la Santé et de la Recherche Médicale U1209, Centre National de la Recherche Scientifique UMR 5309, Université Grenoble Alpes, Grenoble 38000, France; Centre Hospitalier Universitaire de Grenoble, UM GI-DPI, Grenoble 38000, France.
Chunyu LiuObstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai 200011, China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China; State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211116, China.
Charles CouttonGenetic Epigenetic and Therapies of Infertility, Institute for Advanced Biosciences, Institut National de la Santé et de la Recherche Médicale U1209, Centre National de la Recherche Scientifique UMR 5309, Université Grenoble Alpes, Grenoble 38000, France; Centre Hospitalier Universitaire de Grenoble, UM de Génétique Chromosomique, Grenoble 38000, France.
Rui ZhaoObstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai 200011, China.
Dongdong TangReproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, Hefei 230022, China; Anhui Provincial Engineering Technology Research Center for Biopreservation and Artificial Organs, Hefei 230022, China.
Shuyan TangObstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai 200011, China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China.
Mingrong LvReproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, Hefei 230022, China; Anhui Provincial Engineering Technology Research Center for Biopreservation and Artificial Organs, Hefei 230022, China.
Youyan FangReproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, Hefei 230022, China; Anhui Provincial Engineering Technology Research Center for Biopreservation and Artificial Organs, Hefei 230022, China.
Weiyu LiObstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai 200011, China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China; State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211116, China.
Hong LiState Key Laboratory of Reproductive Medicine, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215002, China; Suzhou Municipal Hospital, Suzhou 215002, China.
Jianyuan ZhaoObstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai 200011, China.
Xue WangDepartment of Gynecology and Obstetrics, the Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China.
Shimin ZhaoObstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai 200011, China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China.
Jingjing ZhangReproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, Hefei 230022, China; Anhui Provincial Engineering Technology Research Center for Biopreservation and Artificial Organs, Hefei 230022, China.
Christophe ArnoultGenetic Epigenetic and Therapies of Infertility, Institute for Advanced Biosciences, Institut National de la Santé et de la Recherche Médicale U1209, Centre National de la Recherche Scientifique UMR 5309, Université Grenoble Alpes, Grenoble 38000, France.
Li JinObstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai 200011, China.
Zhiguo ZhangReproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, Hefei 230022, China; Anhui Provincial Engineering Technology Research Center for Biopreservation and Artificial Organs, Hefei 230022, China.
Pierre F RayGenetic Epigenetic and Therapies of Infertility, Institute for Advanced Biosciences, Institut National de la Santé et de la Recherche Médicale U1209, Centre National de la Recherche Scientifique UMR 5309, Université Grenoble Alpes, Grenoble 38000, France; Centre Hospitalier Universitaire de Grenoble, UM GI-DPI, Grenoble 38000, France.
Yunxia CaoReproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, Hefei 230022, China; Anhui Provincial Engineering Technology Research Center for Biopreservation and Artificial Organs, Hefei 230022, China. Electronic address: caoyunxia6@126.com.
Feng ZhangObstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai 200011, China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China; State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211116, China; Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China. Electronic address: zhangfeng@fudan.edu.cn.
Anhui Medical University · CNFudan University · CNInserm · FRSuzhou Municipal Hospital · CN
Funding
No grant is acknowledged in the PubMed record.
Abstract
Male infertility is a major concern affecting human reproductive health. Asthenoteratospermia can cause male infertility through reduced motility and abnormal morphology of spermatozoa. Several genes, including DNAH1 and some CFAP family members, are involved in multiple morphological abnormalities of the sperm flagella (MMAF). However, these known genes only account for approximately 60% of human MMAF cases. Here, we conducted further genetic analyses by using whole-exome sequencing in a cohort of 65 Han Chinese men with MMAF. Intriguingly, bi-allelic mutations of TTC21A (tetratricopeptide repeat domain 21A) were identified in three (5%) unrelated, MMAF-affected men, including two with homozygous stop-gain mutations and one with compound heterozygous mutations of TTC21A. Notably, these men consistently presented with MMAF and additional abnormalities of sperm head-tail conjunction. Furthermore, a homozygous TTC21A splicing mutation was identified in two Tunisian cases from an independent MMAF cohort. TTC21A is preferentially expressed in the testis and encodes an intraflagellar transport (IFT)-associated protein that possesses several tetratricopeptide repeat domains that perform functions crucial for ciliary function. To further investigate the potential roles of TTC21A in spermatogenesis, we generated Ttc21a mutant mice by using CRISPR-Cas9 technology and revealed sperm structural defects of the flagella and the connecting piece. Our consistent observations across human populations and in the mouse model strongly support the notion that bi-allelic mutations in TTC21A can induce asthenoteratospermia with defects of the sperm flagella and head-tail conjunction.
Indexed as
MutationAllelesAlternative SplicingAnimalsChinaCRISPR-Cas SystemsExomeExome SequencingFlagellaHomozygoteHumansInfertility, MaleMaleMiceMicrotubule-Associated ProteinsPhenotypeMicrotubule-Associated ProteinsTTC21A protein, humanTtc21a protein, mouseCRISPRexomeflagellamale infertilityMMAFsequencingspermTTC21A
Identifiers
What OpenQuestion holds
Textmetadata
Read underepoch 390
Registered trials
None linked
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.