{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:32:56Z","timestamp":1791361976865,"version":"4.3.1"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T00:00:00Z","timestamp":1740441600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,7]]},"abstract":"Abstract<\/jats:title>\n \n Multiple morphological abnormalities of sperm flagella (MMAF) is a severe form of asthenoteratozoospermia, characterized by morphological abnormalities and reduced motility of sperm, causing male infertility. Although approximately 60% of MMAF cases can be explained genetically, the etiology of the remaining cases is unclear. Here, we identified two novel compound heterozygous variants in the gene, dynein axonemal heavy chain 10 (\n DNAH10<\/jats:italic>\n ), in three patients from two unrelated Pakistani families using whole-exome sequencing (WES), including one compound heterozygous mutation (\n DNAH10<\/jats:italic>\n : c.9409C>A [p.P3137T]; c.12946G>C [p.D4316H]) in family 1 and another compound heterozygous mutation (\n DNAH10<\/jats:italic>\n : c.8849G>A [p.G2950D]; c.11509C>T [p.R3687W]) in family 2. All the identified variants are absent or rare in public genome databases and are predicted to have deleterious effects according to multiple bioinformatic tools. Sanger sequencing revealed that these variants follow an autosomal recessive mode of inheritance. Hematoxylin and eosin (H&E) staining revealed MMAF, including sperm head abnormalities, in the patients. In addition, immunofluorescence staining revealed loss of DNAH10 protein signals along sperm flagella. These findings broaden the spectrum of\n DNAH10<\/jats:italic>\n variants and expand understanding of the genetic basis of male infertility associated with the MMAF phenotype.\n <\/jats:p>","DOI":"10.4103\/aja2024116","type":"journal-article","created":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T06:00:13Z","timestamp":1740463213000},"page":"516-523","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":6,"title":["Novel bi-allelic variants in DNAH10 lead to multiple morphological abnormalities of sperm flagella and male infertility"],"prefix":"10.4103","volume":"27","author":[{"given":"Muhammad","family":"Shoaib","sequence":"first","affiliation":[{"name":"Center for Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Zubair","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wasim","family":"Shah","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meftah","family":"Uddin","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ansar","family":"Hussain","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghulam","family":"Mustafa","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fazal","family":"Rahim","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imtiaz","family":"Ali","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanveer","family":"Abbas","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousaf","family":"Raza","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sui-Xing","family":"Fan","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing-Hua","family":"Shi","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Research Center for Physical Sciences at the Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, Institute of Health and Medicine, Hefei Comprehensive National Science Center, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,2,25]]},"reference":[{"key":"R1-20250716","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/s10815-021-02306-x","article-title":"Bi-allelic variants in DNAH10 cause asthenoteratozoospermia and male infertility","volume":"39","author":"Li","year":"2022","journal-title":"J Assist Reprod Genet"},{"key":"R2-20250716","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.ajhg.2013.11.017","article-title":"Mutations in DNAH1, which encodes an inner arm heavy chain dynein, lead to male infertility from multiple morphological abnormalities of the sperm flagella","volume":"94","author":"Ben Khelifa","year":"2014","journal-title":"Am J Hum Genet"},{"key":"R3-20250716","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/s41421-021-00327-5","article-title":"Bi-allelic variants in human WDR63 cause male infertility via abnormal inner dynein arms assembly","volume":"7","author":"Lu","year":"2021","journal-title":"Cell Discov"},{"key":"R4-20250716","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.beem.2010.08.006","article-title":"Male infertility:pathogenesis and clinical diagnosis","volume":"25","author":"Krausz","year":"2011","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"R5-20250716","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1080\/14737159.2018.1453358","article-title":"Testing for genetic contributions to infertility:potential clinical impact","volume":"18","author":"Krausz","year":"2018","journal-title":"Expert Rev Mol Diagn"},{"key":"R6-20250716","doi-asserted-by":"crossref","first-page":"662903","DOI":"10.3389\/fcell.2021.662903","article-title":"Genetic defects in DNAH2 underlie male infertility with multiple morphological abnormalities of the sperm flagella in humans and mice","volume":"9","author":"Hwang","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"R7-20250716","doi-asserted-by":"crossref","first-page":"hoae003","DOI":"10.1093\/hropen\/hoae003","article-title":"Bi-allelic variants in DNAH3 cause male infertility with asthenoteratozoospermia in humans and mice","author":"Meng","year":"2024","journal-title":"Hum Reprod Open 2024"},{"key":"R8-20250716","doi-asserted-by":"crossref","first-page":"15864","DOI":"10.1038\/s41598-019-52436-7","article-title":"Identification of DNAH6 mutations in infertile men with multiple morphological abnormalities of the sperm flagella","volume":"9","author":"Tu","year":"2019","journal-title":"Sci Rep"},{"key":"R9-20250716","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s12958-021-00709-0","article-title":"Novel variants in DNAH9 lead to nonsyndromic severe asthenozoospermia","volume":"19","author":"Tang","year":"2021","journal-title":"Reprod Biol Endocrinol"},{"key":"R10-20250716","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.ajhg.2020.06.004","article-title":"Bi-allelic DNAH8 variants lead to multiple morphological abnormalities of the sperm flagella and primary male infertility","volume":"107","author":"Liu","year":"2020","journal-title":"Am J Hum Genet"},{"key":"R11-20250716","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/s41419-023-05653-y","article-title":"DNALI1 deficiency causes male infertility with severe asthenozoospermia in humans and mice by disrupting the assembly of the flagellar inner dynein arms and fibrous sheath","volume":"14","author":"Wu","year":"2023","journal-title":"Cell Death Dis"},{"key":"R12-20250716","doi-asserted-by":"crossref","first-page":"e20182365","DOI":"10.1084\/jem.20182365","article-title":"A DNAH17 missense variant causes flagella destabilization and asthenozoospermia","volume":"217","author":"Zhang","year":"2020","journal-title":"J Exp Med"},{"key":"R13-20250716","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1111\/andr.13287","article-title":"Potential role of dynein-related genes in the etiology of male infertility:a systematic review and a meta-analysis","volume":"10","author":"Levkova","year":"2022","journal-title":"Andrology"},{"key":"R14-20250716","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.ajhg.2019.12.010","article-title":"TTC12 loss-of-function mutations cause primary ciliary dyskinesia and unveil distinct dynein assembly mechanisms in motile cilia versus flagella","volume":"106","author":"Thomas","year":"2020","journal-title":"Am J Hum Genet"},{"key":"R15-20250716","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1016\/j.ajhg.2021.06.010","article-title":"Bi-allelic mutations of DNAH10 cause primary male infertility with asthenoteratozoospermia in humans and mice","volume":"108","author":"Tu","year":"2021","journal-title":"Am J Hum Genet"},{"key":"R16-20250716","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1093\/humrep\/deab229","article-title":"Whole-exome sequencing of a cohort of infertile men reveals novel causative genes in teratozoospermia that are chiefly related to sperm head defects","volume":"37","author":"Li","year":"2022","journal-title":"Hum Reprod"},{"key":"R17-20250716","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1007\/s11684-023-0988-8","article-title":"Dynein axonemal heavy chain 10 deficiency causes primary ciliary dyskinesia in humans and mice","volume":"17","author":"Wang","year":"2023","journal-title":"Front Med"},{"key":"R18-20250716","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/s41585-018-0003-3","article-title":"Genetics of male infertility","volume":"15","author":"Krausz","year":"2018","journal-title":"Nat Rev Urol"},{"key":"R19-20250716","doi-asserted-by":"crossref","first-page":"e166869","DOI":"10.1172\/jci.insight.166869","article-title":"Loss-of-function mutations in CFAP57 cause multiple morphological abnormalities of the flagella in humans and mice","volume":"8","author":"Ma","year":"2023","journal-title":"JCI Insight"},{"key":"R20-20250716","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/s41436-018-0015-7","article-title":"A homozygous FANCM frameshift pathogenic variant causes male infertility","volume":"21","author":"Yin","year":"2019","journal-title":"Genet Med"},{"key":"R22-20250716","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1093\/humrep\/dev251","article-title":"Another look at human sperm morphology","volume":"31","author":"Auger","year":"2016","journal-title":"Hum Reprod"},{"key":"R23-20250716","doi-asserted-by":"crossref","first-page":"W636","DOI":"10.1093\/nar\/gkz268","article-title":"The EMBL-EBI search and sequence analysis tools APIs in 2019","volume":"47","author":"Madeira","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"R24-20250716","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/cr.2009.6","article-title":"DOG 1.0:illustrator of protein domain structures","volume":"19","author":"Ren","year":"2009","journal-title":"Cell Res"},{"key":"R25-20250716","first-page":"Unit7.20","article-title":"Predicting functional effect of human missense mutations using PolyPhen-2","volume":"7","author":"Adzhubei","year":"2013","journal-title":"Curr Protoc Hum Genet"},{"key":"R26-20250716","doi-asserted-by":"crossref","first-page":"W452","DOI":"10.1093\/nar\/gks539","article-title":"SIFT web server:predicting effects of amino acid substitutions on proteins","volume":"40","author":"Sim","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"R27-20250716","doi-asserted-by":"crossref","first-page":"W446","DOI":"10.1093\/nar\/gkab266","article-title":"Mutationtaster 2021","volume":"49","author":"Steinhaus","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"R28-20250716","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1002\/prot.20810","article-title":"Prediction of protein stability changes for single-site mutations using support vector machines","volume":"62","author":"Cheng","year":"2006","journal-title":"Proteins"},{"key":"R29-20250716","doi-asserted-by":"crossref","first-page":"W306","DOI":"10.1093\/nar\/gki375","article-title":"I-Mutant2.0:predicting stability changes upon mutation from the protein sequence or structure","volume":"33","author":"Capriotti","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"R30-20250716","doi-asserted-by":"crossref","first-page":"19136","DOI":"10.1038\/s41598-019-53874-z","article-title":"Discovery of increased epidermal DNAH10 expression after regeneration of dermis in a randomized with-in person trial \u2013reflections on psoriatic inflammation","volume":"9","author":"Lagus","year":"2019","journal-title":"Sci Rep"},{"key":"R32-20250716","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1242\/jcs.111.9.1155","article-title":"Translocation of microtubules caused by the \u03b1\u03b2, \u03b2and \u03b3outer arm dynein subparticles of Chlamydomonas","volume":"111","author":"Sakakibara","year":"1998","journal-title":"J Cell Sci"},{"key":"R33-20250716","doi-asserted-by":"crossref","first-page":"a028100","DOI":"10.1101\/cshperspect.a028100","article-title":"Axonemal dynein arms","volume":"8","author":"King","year":"2016","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"R34-20250716","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1007\/s00418-008-0416-9","article-title":"Structure and function of mammalian cilia","volume":"129","author":"Satir","year":"2008","journal-title":"Histochem Cell Biol"},{"key":"R35-20250716","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1002\/bip.22856","article-title":"Review:structure and mechanism of the dynein motor ATPase","volume":"105","author":"Schmidt","year":"2016","journal-title":"Biopolymers"},{"key":"R36-20250716","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1038\/sj.ejhg.5200555","article-title":"Identification, tissue specific expression, and chromosomal localisation of several human dynein heavy chain genes","volume":"8","author":"Maiti","year":"2000","journal-title":"Eur J Hum Genet"},{"key":"R37-20250716","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1002\/cm.20533","article-title":"A unified taxonomy for ciliary dyneins","volume":"68","author":"Hom","year":"2011","journal-title":"Cytoskeleton (Hoboken)"}],"container-title":["Asian Journal of Andrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/aja2024116","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:24:47Z","timestamp":1787837087000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/aja2024116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,25]]},"references-count":35,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025]]}},"URL":"https:\/\/doi.org\/10.4103\/aja2024116","relation":{},"ISSN":["1745-7262","1008-682X"],"issn-type":[{"value":"1745-7262","type":"print"},{"value":"1008-682X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,25]]},"assertion":[{"value":"2024-06-07","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-03","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}