{
    "abstract": "Multiple morphological abnormalities of the sperm flagella (MMAF) is a subtype of severe asthenoteratozoospermia with poorly understood genetic etiology. SPAG6 is a core axonemal component that plays a critical role in the formation of cilia and sperm flagella. Previous studies have reported that mutations in SPAG6 cause primary ciliary dyskinesia (PCD), but the association between SPAG6 gene variants and the MMAF phenotype has not yet been described.\nWe performed whole-exome sequencing (WES) in two unrelated Han Chinese men with MMAF. Sanger sequencing was used to validate the candidate variants. Routine semen analysis was carried out according to the WHO guidelines (5\nTwo homozygous SPAG6 variants were identified by WES and Sanger validation in two patients with MMAF phenotype (F1 II-1: c.308C\u2009>\u2009A, p. A103D; F2 II-1: c. 585delA, p. K196Sfs*6). Semen analysis showed progressive rates of less than 1%, and most of the spermatozoa presented MMAF by Papanicolaou staining. TEM revealed that the overall axonemal ultrastructure was disrupted and primarily presented an abnormal \"9\u2009+\u20090\" configuration. No other PCD-related symptoms were found on physical examination and medical consultations, as well as lung CT screening. The level of SPAG6 protein was significantly decreased in the spermatozoa, and IF analysis revealed that SPAG6 staining was extremely weak and discontinuous in the sperm flagella of the two patients. Notably, F1 II-1 and his wife conceived successfully after undergoing ICSI.\nOur research provides new evidence for a potential correlation between SPAG6 variants and the MMAF phenotype.",
    "authors": [
        {
            "affiliation": "Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China.\nNHC Key Laboratory of Study On Abnormal Gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei, 230032, Anhui, China.\nKey Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei, 230032, Anhui, China.",
            "firstname": "Chuan",
            "initials": "C",
            "lastname": "Xu"
        },
        {
            "affiliation": "Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China.\nNHC Key Laboratory of Study On Abnormal Gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei, 230032, Anhui, China.\nKey Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei, 230032, Anhui, China.",
            "firstname": "Dongdong",
            "initials": "D",
            "lastname": "Tang"
        },
        {
            "affiliation": "Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China.\nNHC Key Laboratory of Study On Abnormal Gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei, 230032, Anhui, China.\nKey Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei, 230032, Anhui, China.",
            "firstname": "Zhongmei",
            "initials": "Z",
            "lastname": "Shao"
        },
        {
            "affiliation": "Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China.\nAnhui Province Key Laboratory of Reproductive Health and Genetics, No 81 Meishan Road, Hefei, 230032, Anhui, China.\nBiopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China.",
            "firstname": "Hao",
            "initials": "H",
            "lastname": "Geng"
        },
        {
            "affiliation": "Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China.\nAnhui Province Key Laboratory of Reproductive Health and Genetics, No 81 Meishan Road, Hefei, 230032, Anhui, China.\nBiopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China.",
            "firstname": "Yang",
            "initials": "Y",
            "lastname": "Gao"
        },
        {
            "affiliation": "Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China.\nAnhui Province Key Laboratory of Reproductive Health and Genetics, No 81 Meishan Road, Hefei, 230032, Anhui, China.\nBiopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China.",
            "firstname": "Kuokuo",
            "initials": "K",
            "lastname": "Li"
        },
        {
            "affiliation": "Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China.\nAnhui Province Key Laboratory of Reproductive Health and Genetics, No 81 Meishan Road, Hefei, 230032, Anhui, China.\nBiopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China.",
            "firstname": "Qing",
            "initials": "Q",
            "lastname": "Tan"
        },
        {
            "affiliation": "Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China.\nAnhui Province Key Laboratory of Reproductive Health and Genetics, No 81 Meishan Road, Hefei, 230032, Anhui, China.\nBiopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China.",
            "firstname": "Guanxiong",
            "initials": "G",
            "lastname": "Wang"
        },
        {
            "affiliation": "Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China.\nAnhui Province Key Laboratory of Reproductive Health and Genetics, No 81 Meishan Road, Hefei, 230032, Anhui, China.\nBiopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China.",
            "firstname": "Chao",
            "initials": "C",
            "lastname": "Wang"
        },
        {
            "affiliation": "Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China.\nAnhui Province Key Laboratory of Reproductive Health and Genetics, No 81 Meishan Road, Hefei, 230032, Anhui, China.\nBiopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China.",
            "firstname": "Huan",
            "initials": "H",
            "lastname": "Wu"
        },
        {
            "affiliation": "Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China.\nAnhui Province Key Laboratory of Reproductive Health and Genetics, No 81 Meishan Road, Hefei, 230032, Anhui, China.\nBiopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China.",
            "firstname": "Guanjian",
            "initials": "G",
            "lastname": "Li"
        },
        {
            "affiliation": "Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China. lvmingrong2016@163.com.\nAnhui Province Key Laboratory of Reproductive Health and Genetics, No 81 Meishan Road, Hefei, 230032, Anhui, China. lvmingrong2016@163.com.\nBiopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China. lvmingrong2016@163.com.",
            "firstname": "Mingrong",
            "initials": "M",
            "lastname": "Lv"
        },
        {
            "affiliation": "Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China. hxj0117@126.com.\nNHC Key Laboratory of Study On Abnormal Gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei, 230032, Anhui, China. hxj0117@126.com.\nKey Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei, 230032, Anhui, China. hxj0117@126.com.",
            "firstname": "Xiaojin",
            "initials": "X",
            "lastname": "He"
        },
        {
            "affiliation": "Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China. caoyunxia6@126.com.\nNHC Key Laboratory of Study On Abnormal Gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei, 230032, Anhui, China. caoyunxia6@126.com.\nKey Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei, 230032, Anhui, China. caoyunxia6@126.com.",
            "firstname": "Yunxia",
            "initials": "Y",
            "lastname": "Cao"
        }
    ],
    "conclusions": null,
    "copyrights": "\u00a9 2022. The Author(s).",
    "doi": "10.1186/s12958-022-00916-3\n10.1016/j.clinbiochem.2018.03.012\n10.18632/aging.102497\n10.1186/s12958-015-0032-1\n10.1038/s41585-018-0003-3\n10.1016/j.ajhg.2013.11.017\n10.1093/humupd/dmv020\n10.1016/j.ajhg.2020.06.004\n10.1136/jmedgenet-2019-106011\n10.1016/j.ajhg.2018.12.013\n10.1007/s10815-020-01770-1\n10.1016/j.ajhg.2019.10.007\n10.1016/j.ajhg.2019.10.010\n10.1006/geno.1999.5914\n10.1007/s10815-020-01721-w\n10.1128/MCB.22.17.6298-6305.2002\n10.1016/j.ajhg.2017.04.012\n10.1093/humupd/dmp048\n10.1136/jmedgenet-2019-106479\n10.1136/jmedgenet-2018-105486\n10.1016/j.ajhg.2018.06.010\n10.1101/cshperspect.a028076\n10.1083/jcb.91.1.69\n10.1083/jcb.132.3.359\n10.1186/s12958-021-00709-0\n10.1073/pnas.0402354101\n10.1038/ncomms4230",
    "journal": "Reproductive biology and endocrinology : RB&E",
    "keywords": [
        "Asthenoteratozoospermia",
        "Gene",
        "ICSI",
        "MMAF",
        "SPAG6"
    ],
    "methods": null,
    "publication_date": "2022-03-03",
    "pubmed_id": "35232447\n29555319\n31790362\n25928197\n29622783\n24360805\n25888788\n32619401\n31048344\n30686508\n32323121\n31735292\n31735294\n10493827\n32124190\n12167721\n28552195\n19934213\n32051257\n30415212\n30032984\n27601632\n7028763\n8636214\n28577616\n33610189\n15173597\n24510058",
    "results": "Two homozygous SPAG6 variants were identified by WES and Sanger validation in two patients with MMAF phenotype (F1 II-1: c.308C\u2009>\u2009A, p. A103D; F2 II-1: c. 585delA, p. K196Sfs*6). Semen analysis showed progressive rates of less than 1%, and most of the spermatozoa presented MMAF by Papanicolaou staining. TEM revealed that the overall axonemal ultrastructure was disrupted and primarily presented an abnormal \"9\u2009+\u20090\" configuration. No other PCD-related symptoms were found on physical examination and medical consultations, as well as lung CT screening. The level of SPAG6 protein was significantly decreased in the spermatozoa, and IF analysis revealed that SPAG6 staining was extremely weak and discontinuous in the sperm flagella of the two patients. Notably, F1 II-1 and his wife conceived successfully after undergoing ICSI.",
    "title": "Homozygous SPAG6 variants can induce nonsyndromic asthenoteratozoospermia with severe MMAF.",
    "xml": "<Element 'PubmedArticle' at 0x788502a23d80>"
}