{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTSPYL1 is an evolutionarily young member of the nucleosome assembly protein (NAP) family that plays a critical role in chromatin remodeling and the regulation of gene expression. In erythroid cells, its expression is modulated in disorders of hemoglobin production; for example, increased TSPYL1 levels in hereditary persistence of fetal hemoglobin (HPFH) versus reduced levels in deltabeta‐thalassemia suggest that it may contribute to the pancellular versus heterocellular distribution of fetal hemoglobin by influencing chromatin accessibility at globin gene loci."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic studies have further implicated TSPYL1 in testicular development and male reproductive function. Loss‐of‐function mutations in TSPYL1 were first reported in infants with sudden death accompanied by gonadal dysgenesis, defining the syndrome known as sudden infant death with dysgenesis of the testes (SIDDT)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Subsequent reports identified missense mutations in individuals with anomalies of testicular development and idiopathic male infertility"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", while additional screening in cohorts with spermatogenic failure established an association between rare TSPYL1 variants and impaired sperm production."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Nonetheless, studies in other populations, such as a Swiss SIDS cohort, did not detect a significant link between TSPYL1 variants and the sudden infant death syndrome."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, TSPYL1 deficiency has been shown to cause a multisystem disorder that combines nervous system abnormalities with reproductive defects. A recent study described a family in which a homozygous frameshift mutation in TSPYL1 resulted in neurodevelopmental delays, cell cycle dysregulation, and testicular dysgenesis leading to early, lethal outcomes—a phenotype that was recapitulated in zebrafish morphants."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its roles in development, mechanistic investigations have revealed that TSPYL1 interacts with transcription factors (such as FOXA1) and epigenetic modifiers (including EZH2) to repress targets like TGFBR1, thereby modulating TGFβ signaling and influencing the epithelial—mesenchymal transition (EMT) in cancer cells. Notably, TSPYL1 appears to act in opposition to its family member TSPYL2, forming a counter-balancing network that affects both cell proliferation and signal transduction pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tiago Gomes de Andrade, Kenneth R Peterson, Anderson F Cunha, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of novel candidate genes for globin regulation in erythroid cells containing large deletions of the human beta-globin gene cluster."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood Cells Mol Dis (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bcmd.2006.07.003"}], "href": "https://doi.org/10.1016/j.bcmd.2006.07.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16952470"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16952470"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Robert Hering, Rosario Frade-Martinez, Thomas Bajanowski, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Should TSPYL1 mutation screening be included in routine diagnostics of male idiopathic infertility?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Fertil Steril (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.fertnstert.2011.11.002"}], "href": "https://doi.org/10.1016/j.fertnstert.2011.11.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22137496"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22137496"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Xiling Yang, Xiangyou Leng, Wenling Tu, et al. 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