{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DNAH8 encodes a dynein axonemal heavy chain that plays a critical role in the formation and function of motile cilia and flagella. In the male reproductive system, DNAH8 is preferentially expressed in the testis and localizes along the sperm flagellum, where it participates in the assembly and function of the outer dynein arm motor complexes. Loss‐of‐function mutations or splicing defects in DNAH8 lead to multiple morphological abnormalities of the sperm flagella (MMAF), resulting in reduced sperm motility and male infertility manifested as asthenozoospermia or asthenoteratospermia."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its well‐established role in sperm flagellar assembly, DNAH8 is also expressed in prostate tissue where it functions as a novel regulator of androgen receptor (AR) signaling. Androgen exposure upregulates DNAH8 expression, and enhanced levels of DNAH8 in prostate cancer are correlated with increased AR transcriptional activity, tumor cell proliferation, and metastasis, ultimately contributing to poor patient prognosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, somatic mutations in DNAH8 have been identified in other malignancies—including hepatocellular carcinoma and inflammatory breast cancer—suggesting that aberrations in DNAH8 may contribute to tumorigenesis outside the reproductive system."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, exome sequencing studies in patients with substance use disorders have identified variants in DNAH8, implying that the gene may have broader roles in cellular physiology that extend beyond ciliogenesis and sperm motility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Marjorie Whitfield, Lucie Thomas, Emilie Bequignon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in DNAH17, Encoding a Sperm-Specific Axonemal Outer Dynein Arm Heavy Chain, Cause Isolated Male Infertility Due to Asthenozoospermia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2019.04.015"}], "href": "https://doi.org/10.1016/j.ajhg.2019.04.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31178125"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31178125"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Chunyu Liu, Haruhiko Miyata, Yang Gao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bi-allelic DNAH8 Variants Lead to Multiple Morphological Abnormalities of the Sperm Flagella and Primary Male Infertility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2020.06.004"}], "href": "https://doi.org/10.1016/j.ajhg.2020.06.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32619401"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32619401"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yihong Yang, Chuan Jiang, Xueguang Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss-of-function mutation in DNAH8 induces asthenoteratospermia associated with multiple morphological abnormalities of the sperm flagella."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Genet (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cge.13815"}], "href": "https://doi.org/10.1111/cge.13815"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32681648"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32681648"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Mingxiang Weng, Yanwei Sha, Y U Zeng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in DNAH8 contribute to multiple morphological abnormalities of sperm flagella and male infertility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Biochim Biophys Sin (Shanghai) (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/abbs/gmab013"}], "href": "https://doi.org/10.1093/abbs/gmab013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33704367"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33704367"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Zhou Zhou, Xiaoyan Mao, Biaobang Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel splicing variant in DNAH8 causes asthenozoospermia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Assist Reprod Genet (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10815-021-02116-1"}], "href": "https://doi.org/10.1007/s10815-021-02116-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33611675"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33611675"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Lucile Ferreux, Mathilde Bourdon, Ahmed Chargui, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic diagnosis, sperm phenotype and ICSI outcome in case of severe asthenozoospermia with multiple morphological abnormalities of the flagellum."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Reprod (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/humrep/deab200"}], "href": "https://doi.org/10.1093/humrep/deab200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34529793"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34529793"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yu Wang, Russell J Ledet, Keren Imberg-Kazdan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dynein axonemal heavy chain 8 promotes androgen receptor activity and associates with prostate cancer progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.10284"}], "href": "https://doi.org/10.18632/oncotarget.10284"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27363033"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27363033"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Feifeng Song, Yiwen Zhang, Zongfu Pan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of novel key genes associated with the metastasis of prostate cancer based on bioinformatics prediction and validation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell Int (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12935-021-02258-3"}], "href": "https://doi.org/10.1186/s12935-021-02258-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34696780"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34696780"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Fangyuan Dong, Qin Yang, Zheng Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of survival-related predictors in hepatocellular carcinoma through integrated genomic, transcriptomic, and proteomic analyses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Pharmacother (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biopha.2019.108856"}], "href": "https://doi.org/10.1016/j.biopha.2019.108856"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30981109"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30981109"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Rui Luo, Weelic Chong, Qiang Wei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Whole-exome sequencing identifies somatic mutations and intratumor heterogeneity in inflammatory breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "NPJ Breast Cancer (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41523-021-00278-w"}], "href": "https://doi.org/10.1038/s41523-021-00278-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34075047"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34075047"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "P V AshaRani, Syidda Amron, Noor Azizah Bte Zainuldin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Whole-Exome Sequencing to Identify Potential Genetic Risk in Substance Use Disorders: A Pilot Feasibility Study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Med (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/jcm10132810"}], "href": "https://doi.org/10.3390/jcm10132810"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34202351"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34202351"}]}]}]}