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The underlying mechanism of HM remains elusive. Given the extensive genetic heterogeneity and vast genetic base opacity, it is imperative to identify more causative genes and explore their pathogenic roles in HM.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>We employed exome sequencing to pinpoint the causal gene in an HM family. Sanger sequencing was used to confirm and analyse the gene mutations in this family and 200 sporadic HM cases. Single-cell RNA sequencing was conducted to evaluate the gene\u2019s expression patterns in developing human and mouse retinas. The CRISPR\/Cas9 system facilitated the gene knockout cells, aiding in the exploration of the gene\u2019s function and its mutations. Immunofluorescent staining and immunoblot techniques were applied to monitor the functional shifts of the gene mutations at the cellular level.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>\nA suspected nonsense mutation (c.C172T, p.Q58X) in\n<jats:italic>CCDC66<\/jats:italic>\nwas found to be co-segregated with the HM phenotype in the family. Additionally, six other rare variants were identified among the 200 sporadic patients.\n<jats:italic>CCDC66<\/jats:italic>\nwas consistently expressed in the embryonic retinas of both humans and mice. Notably, in CCDC66-deficient HEK293 cells, there was a decline in cell proliferation, microtube polymerisation rate and ace-tubulin level. Furthermore, the mutated CCDC66 failed to synchronise with the tubulin system during Hela cell mitosis, unlike its wild type counterpart.\n<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>\nOur research indicates that the\n<jats:italic>CCDC66<\/jats:italic>\nvariant c.C172T is associated with HM. A deficiency in CCDC66 might disrupt cell proliferation by influencing the mitotic process during retinal growth, leading to HM.\n<\/jats:p>\n<\/jats:sec>","DOI":"10.1136\/jmg-2023-109434","type":"journal-article","created":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T17:21:55Z","timestamp":1697649715000},"page":"262-269","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["<i>CCDC66<\/i>\nmutations are associated with high myopia through affected cell mitosis"],"prefix":"10.1136","volume":"61","author":[{"given":"Xiaozhen","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Tong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhe","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liyu","family":"Zang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhikuan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weizhong","family":"Lan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kun","family":"Xia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3921-8205","authenticated-orcid":false,"given":"Zhengmao","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0798-2759","authenticated-orcid":false,"given":"Qi","family":"Tian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2023,10,18]]},"reference":[{"key":"2024091209100813000_61.3.262.1","unstructured":"Organization WH . 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