{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:38:27Z","timestamp":1790818707307,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","license":[{"start":{"date-parts":[[2019,10,3]],"date-time":"2019-10-03T00:00:00Z","timestamp":1570060800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81700793"],"award-info":[{"award-number":["81700793"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["SYS 201561"],"award-info":[{"award-number":["SYS 201561"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Suzhou Science and Technology Development Project","award":["81700793"],"award-info":[{"award-number":["81700793"]}]},{"name":"Suzhou Science and Technology Development Project","award":["SYS 201561"],"award-info":[{"award-number":["SYS 201561"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["International Journal of Endocrinology"],"published-print":{"date-parts":[[2019,10,3]]},"abstract":"<jats:p><jats:italic>Background<\/jats:italic>. Central precocious puberty (CPP) is defined by gonadotropin-dependent development of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys. <jats:italic>MKRN3<\/jats:italic> and <jats:italic>DLK1<\/jats:italic> are two genes, disease-causing variants of which have recently been discovered to cause idiopathic CPP. <jats:italic>Methods<\/jats:italic>. We screened 173 Chinese patients (9 males and 164 females; 9 familial and 164 sporadic) with ICPP and 43 patients (9 males and 34 females; 3 familial and 40 sporadic) with early puberty for variants in <jats:italic>MKRN3<\/jats:italic>. We also screened 19 patients with ICPP and early puberty for variants of <jats:italic>DLK1<\/jats:italic> (17 males and 2 females; 5 familial and 14 sporadic). <jats:italic>Results<\/jats:italic>. We identified four novel missense variants of <jats:italic>MKRN3<\/jats:italic>, c.1138G\u2009&gt;\u2009A (p.Glu380Lys), c.1420T\u2009&gt;\u2009A (p.Leu474Met), c.673C\u2009&gt;\u2009G (p.Leu225Val), and c.1071C\u2009&gt;\u2009G (p.Ile357Met) in two sporadic cases and three familial cases. According to ACMG standards, two <jats:italic>MKRN3<\/jats:italic> variant (p.Glu380Lys and p.Ile357Met) are likely pathogenic, and two others are of uncertain significance. We also performed bioinformatic analysis to evaluate the impact of variants on MKRN3 protein structures, which showed that Ile357Met locates at the zinc-binding region (C3HC4 RING finger motif), while Glu380Lys is spatially extremely close to the C3HC4 RING finger, MKRN-specific Cys-His domain, and the third C3H1 zinc-finger motif region. Per Glu380Lys, Glu with negative charges has been changed into Lys with positive charges, which may affect the hydrogen bond formation between amino acids and the stability of the local structure, thus affecting the binding of zinc iron to MKRN3 protein. Besides, we did not identify any variants of <jats:italic>DLK1<\/jats:italic> gene in our patients. <jats:italic>Conclusions<\/jats:italic>. In this study, we report four novel <jats:italic>MKRN3<\/jats:italic> variants in patients with ICPP. Moreover, we did not find any variants of <jats:italic>DLK1<\/jats:italic> gene. Variants of <jats:italic>MKRN3<\/jats:italic> are relatively uncommon in Chinese ICPP patients.<\/jats:p>","DOI":"10.1155\/2019\/9879367","type":"journal-article","created":{"date-parts":[[2019,10,3]],"date-time":"2019-10-03T19:30:56Z","timestamp":1570131056000},"page":"1-6","source":"Crossref","is-referenced-by-count":10,"title":["Low Frequency of MKRN3 and DLK1 Variants in Chinese Children with Central Precocious Puberty"],"prefix":"10.1155","volume":"2019","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0179-3586","authenticated-orcid":true,"given":"Ting","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Genetics and Metabolism, Children\u2019s Hospital of Soochow University, Suzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1763-630X","authenticated-orcid":true,"given":"Linqi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Genetics and Metabolism, Children\u2019s Hospital of Soochow University, Suzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8751-4407","authenticated-orcid":true,"given":"Haiying","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Genetics and Metabolism, Children\u2019s Hospital of Soochow University, Suzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0305-4752","authenticated-orcid":true,"given":"Rongrong","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Genetics and Metabolism, Children\u2019s Hospital of Soochow University, Suzhou, Jiangsu, 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