{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:52:11Z","timestamp":1787017931205,"version":"build-2736575974"},"reference-count":40,"publisher":"S. Karger AG","issue":"11-12","license":[{"start":{"date-parts":[[2019,11,15]],"date-time":"2019-11-15T00:00:00Z","timestamp":1573776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2019,11,15]],"date-time":"2019-11-15T00:00:00Z","timestamp":1573776000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuroendocrinology"],"published-print":{"date-parts":[[2020]]},"abstract":"<b><i>Introduction:<\/i><\/b> Constitutional delay of growth and puberty (CDGP) is the most prevalent cause of delayed puberty in both sexes. Family history of delayed puberty (2 or more affected members in a family) has been evidenced in 50\u201375% of patients with CDGP and the inheritance is often consistent with autosomal dominant pattern, with or without complete penetrance. However, the molecular basis of CDGP is not completely understood. <b><i>Objective:<\/i><\/b> To characterize the clinical and genetic features of a CDGP cohort. <b><i>Methods:<\/i><\/b> Fifty-nine patients with CDGP (48 boys and 11 girls) underwent careful and long-term clinical evaluation. Genetic analysis was performed using a custom DNA target enrichment panel designed to capture 36 known and candidate genes implicated with pubertal development. <b><i>Results:<\/i><\/b> All patients had spontaneous or induced pubertal development (transient hormonal therapy) prior to 18 years of age. The mean clinical follow-up time was 46 \u00b1 28 months. Male predominance (81%), short stature (91%), and family history of delayed puberty (59%) were the main clinical features of this CDGP \u00adcohort. Genetic analyses revealed 15 rare heterozygous missense variants in 15 patients with CDGP (25%) in seven different genes (<i>IGSF10<\/i>, <i>GHSR<\/i>, <i>CHD7<\/i>, <i>SPRY4, WDR11, SEMA3A<\/i>,<i><\/i>and <i>IL17RD<\/i>). <i>IGSF10<\/i> and <i>GHSR<\/i> were the most prevalent affected genes in this group. <b><i>Conclusions:<\/i><\/b> Several rare dominant variants in genes implicated with GnRH migration and metabolism were identified in a quarter of the patients with familial or sporadic CDGP, suggesting genetic heterogeneity in this frequent pediatric condition.<\/jats:p>","DOI":"10.1159\/000504783","type":"journal-article","created":{"date-parts":[[2019,11,15]],"date-time":"2019-11-15T17:06:24Z","timestamp":1573837584000},"page":"959-966","source":"Crossref","is-referenced-by-count":19,"title":["Clinical and Genetic Characterization of a Constitutional Delay of Growth and Puberty 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