{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T08:39:51Z","timestamp":1790498391573,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,7,11]],"date-time":"2020-07-11T00:00:00Z","timestamp":1594425600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Minichromosome maintenance complex component 8 (MCM8) is responsible for homologous recombination and DNA double\u2010strand breaks (DSBs) repair and is the cause of primary ovarian insufficiency (POI), which is seldom diagnosed in adolescents and children.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole\u2010exome sequencing was performed in a 13\u2010year\u2010old girl, and Sanger sequencing was used to identify potentially pathogenic variants in her sister (aged 6\u00a0years and 7\u00a0months) and parents. To identify potential pathogenic mutations, DSBs were induced by mitomycin C (MMC), and the DNA repair capacity was evaluated by the histone H2AX phosphorylation level.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two novel mutations of <jats:italic>MCM8<\/jats:italic>, i.e., c.724T&gt;C (p.C242R) and c.1334C&gt;A (p.S445*), were identified in a 13\u2010year\u2010old girl with POI who exhibited disappeared bilateral ovaries and short stature (height standard difference score [HtSDS]\u00a0=\u00a0\u22123.05), and her sister (aged 6\u00a0years and 7\u00a0months) with progressive POI whose ovary size decreased from normal to unclear and height growth gradually slowed. In the functional experiments, compared with the wild\u2010type, HeLa cells overexpressing mutant p.C242R and p.S445* showed a higher sensitivity to MMC. Furthermore, the mutant p.S445* has a more deleterious effect on DNA damage repair.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results reveal that affected children with the novel pathogenetic mutations p.C242R and p.S445* in the <jats:italic>MCM8<\/jats:italic> gene are characterized by POI, short stature, cancer susceptibility, and genomic instability.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1396","type":"journal-article","created":{"date-parts":[[2020,7,11]],"date-time":"2020-07-11T20:55:45Z","timestamp":1594500945000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Two novel mutations in the <i>MCM8<\/i> gene shared by two Chinese siblings with primary ovarian insufficiency and short stature"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3984-2729","authenticated-orcid":false,"given":"Fei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Endocrinology Shanghai Children\u2019s Hospital Shanghai Jiao Tong University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Shanghai Children\u2019s Hospital Shanghai Jiao Tong University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Shanghai Children\u2019s Hospital Shanghai Jiao Tong University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci78473"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2017.07.015"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu041"},{"issue":"2","key":"e_1_2_10_5_1","first-page":"576","article-title":"MCM8 and MCM9 nucleotide variants in women with primary ovarian insufficiency","volume":"102","author":"Desai S.","year":"2017","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10815\u2010018\u20101325\u2010z"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2016.08.018"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12736"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergen.2015.10.001"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/mop.0000000000000236"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.14768"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpag.2017.07.005"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2012.05.048"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-26666-4_1"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmv036"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102014\u2010102921"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2016\u20101047"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bulcan.2017.09.004"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.11.002"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrgentox.2015.11.004"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.14887"}],"container-title":["Molecular Genetics &amp; 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