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Genetic factor has been considered as the major cause for early\u2010onset high myopia (eoHM), but exact genetic defects for most eoHM are yet to be identified. Through multi\u2010step bioinformatics analysis of our in\u2010house whole exome sequencing dataset from 6397 individuals, variants from 928 probands with eoHM were further compared with those from in\u2010house controls as well as gnomAD database. The results showed that loss\u2010of\u2010function (LoF) variants in a novel gene <jats:italic>HNRNPH1<\/jats:italic> were identified in two of 928 probands with eoHM but in none of 5469\u00a0probands with other eye conditions (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.02). LoF variants in <jats:italic>HNRNPH1<\/jats:italic> were extremely rare and intolerant, while two LoF variants in 928 eoHM were statistically higher than their frequency in gnomAD (<jats:italic>p<\/jats:italic>\u00a0=\u00a05.98\u2009\u00d7\u200910<jats:sup>\u22124<\/jats:sup>). These two LoF variants, c.2dup\/p.(M1?) and c.121dup\/p.(Q41Pfs*20), were absent from existing database. Variants in <jats:italic>HNRNPH1<\/jats:italic> have not been associated with any inherited eye disease before. Expression of HNRNPH1 was enriched in ganglion cell layer and inner nuclear layer in humans. Knockdown of <jats:italic>hnrnph1<\/jats:italic> in zebrafish resulted in ocular coloboma. All these suggest that <jats:italic>HNRNPH1<\/jats:italic> is potential contribution to eoHM when mutated.<\/jats:p>","DOI":"10.1111\/cge.14213","type":"journal-article","created":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T07:04:56Z","timestamp":1661151896000},"page":"424-433","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Variants in <i>HNRNPH1<\/i> are associated with high myopia in humans and ocular coloboma in zebrafish"],"prefix":"10.1111","volume":"102","author":[{"given":"Jiamin","family":"Ouyang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat\u2010sen University Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiqiang","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat\u2010sen University Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenmin","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat\u2010sen University Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueshan","family":"Xiao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat\u2010sen University Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingwei","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat\u2010sen University Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat\u2010sen University Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7508-848X","authenticated-orcid":false,"given":"Qingjiong","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat\u2010sen University Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,8,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.61.4.49"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003299"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2554"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.18-25965"},{"key":"e_1_2_8_6_1","doi-asserted-by":"crossref","unstructured":"Zhang Q. 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