{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMEI1 is a pivotal gene required for proper meiotic progression, with its protein product playing an essential role in orchestrating the initiation and maintenance of meiotic processes, including the formation and regulated repair of DNA double‐strand breaks and homologous chromosome synapsis. Evidence from a mouse model originally characterized by meiotic arrest and azoospermia highlighted that disruption of Mei1 function results in an arrest during meiosis, and subsequent human studies have confirmed that MEI1 is predominantly expressed in the testis. In European American men with azoospermia caused by early meiotic arrest, specific coding single-nucleotide polymorphisms in MEI1 are significantly associated with the infertile phenotype."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Moreover, a homozygous missense mutation in MEI1 has been identified in two brothers with non-obstructive azoospermia, linking a defective MEI1 protein to impaired double-strand break formation and faulty chromosomal synapsis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ", while further studies in Chinese patients demonstrated that bi-allelic deleterious variants in MEI1 resulted in arrest at the spermatocyte stage, underscoring its critical role in maintaining the genomic integrity of germ cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its established function in male meiosis, emerging clinical data also implicate MEI1 in female reproductive outcomes. A case report has expanded the mutational spectrum of MEI1 by describing a female patient with embryonic arrest and recurrent implantation failure, wherein novel frameshift mutations were associated with extensive aneuploidy and aberrant DNA methylation patterns in early embryos. This observation suggests that, in females, MEI1 dysfunction might lead to the extrusion of all maternal chromosomes or other defects in early embryogenesis, providing novel insights into divergent disease mechanisms linked to MEI1 mutations."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hisashi Sato, Toshinobu Miyamoto, Leah Yogev, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polymorphic alleles of the human MEI1 gene are associated with human azoospermia by meiotic arrest."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hum Genet (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10038-006-0394-5"}], "href": "https://doi.org/10.1007/s10038-006-0394-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16683055"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16683055"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "M Ben Khelifa, F Ghieh, R Boudjenah, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A MEI1 homozygous missense mutation associated with meiotic arrest in a consanguineous family."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Reprod (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/humrep/dey073"}], "href": "https://doi.org/10.1093/humrep/dey073"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29659827"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29659827"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yuxiang Zhang, Na Li, Zhiyong Ji, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bi-allelic MEI1 variants cause meiosis arrest and non-obstructive azoospermia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hum Genet (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s10038-023-01119-3"}], "href": "https://doi.org/10.1038/s10038-023-01119-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36759719"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36759719"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jie Dong, Hong Zhang, Xiaoyan Mao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel biallelic mutations in MEI1: expanding the phenotypic spectrum to human embryonic arrest and recurrent implantation failure."}]}, {"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/deab118"}], "href": "https://doi.org/10.1093/humrep/deab118"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34037756"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34037756"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Xiangli Wu, Yuqing Tian, Yiqi Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel MEI1 mutations cause chromosomal and DNA methylation abnormalities leading to embryonic arrest and implantation failure."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Genomics (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00438-024-02113-w"}], "href": "https://doi.org/10.1007/s00438-024-02113-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38416203"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38416203"}]}]}]}