Clinical and Genetic Characterization of a Constitutional Delay of Growth and Puberty Cohort

Autor(es)

Barroso, Priscila Sales ; Lima Jorge, Alexander Augusto ; Lerario, Antonio Marcondes ; Montenegro, Luciana Ribeiro ; Vasques, Gabriela Andrade ; Lima Amato, Lorena Guimaraes ; Gontijo Silveira, Leticia Ferreira ; Mendonca, Berenice Bilharinho ; Latronico, Ana Claudia

• Tipo de documento: Artigo Científico
• Fonte: Neuroendocrinology; v. 110, n. 11-12, p. 8-pg., 2020-10-01.

Resumo

Introduction: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 50-75% 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.Objective:To characterize the clinical and genetic features of a CDGP cohort.Methods: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.Results: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 +/- 28 months. Male predominance (81%), short stature (91%), and family history of delayed puberty (59%) were the main clinical features of this CDGP -cohort. Genetic analyses revealed 15 rare heterozygous missense variants in 15 patients with CDGP (25%) in seven different genes (IGSF10,GHSR,CHD7,SPRY4, WDR11, SEMA3A,andIL17RD).IGSF10andGHSRwere the most prevalent affected genes in this group.Conclusions: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. (AU)

• Processo FAPESP: 13/03236-5 - Novas abordagens e metodologias na investigação genético-molecular dos distúrbios de crescimento e desenvolvimento puberal
• Beneficiário: Alexander Augusto de Lima Jorge
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 14/50137-5 - Caracterização molecular de doenças monogênicas do desenvolvimento por sequenciamento em larga escala
• Beneficiário: Berenice Bilharinho de Mendonça
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários