Absence of Functional LIN28B Mutations in a Large Cohort of Patients with Idiopathic Central Precocious Puberty

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Silveira-Neto, Acacio P. ^[1] ; Leal, Leticia Ferro ^[2] ; Emerman, Amy B. ^[3] ; Henderson, Katherine D. ^[4] ; Piskounova, Elena ^[3] ; Henderson, Brian E. ^[5] ; Gregory, Richard I. ^[3] ; Silveira, Leticia F. Gontijo ^[1] ; Hirschhorn, Joel N. ^{[6, 7, 8, 9]} ; Nguyen, Thutrang T. ^{[6, 7]} ; Beneduzzi, Daiane ^[1] ; Tusset, Cintia ^[1] ; Reis, Ana Claudia S. ^[2] ; Brito, Vinicius N. ^[1] ; Mendonca, Berenice B. ^[1] ; Palmert, Mark R. ^{[10, 11]} ; Antonini, Sonir R. ^[2] ; Latronico, Ana Claudia ^[1]

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^[1] Univ Sao Paulo, Hosp Clin, Fac Med, Lab Hormonios & Genet Mol LIM42, Unidade Endocrinol Desenvolvimento, BR-05508 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Puericultura & Pediat, Sao Paulo - Brazil

^[3] Harvard Univ, Sch Med, Childrens Hosp, Dept Biol Chem & Mol Pharmacol, Stem Cell Program, Cambridge, MA 02138 - USA

^[4] City Hope Natl Med Ctr, Dept Populat Sci, Duarte, CA 91010 - USA

^[5] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 - USA

^[6] Childrens Hosp Boston, Div Genet & Ctr Basic & Translat Obes Res, Boston, MA - USA

^[7] Cambridge Ctr, Cambridge, MA - USA

^[8] Harvard Univ, Sch Med, Dept Genet, Cambridge, MA 02138 - USA

^[9] Childrens Hosp, Div Endocrinol, Boston, MA 02115 - USA

^[10] Univ Toronto, Div Endocrinol, Toronto, ON - Canada

^[11] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8 - Canada

• Tipo de documento: Artigo Científico
• Fonte: Hormone Research in Paediatrics; v. 78, n. 3, p. 144-150, 2012.
• Citações Web of Science: 17

Resumo

Aim: To investigate LIN28B gene variants in children with idiopathic central precocious puberty (CPP). Patients and Methods: We studied 178 Brazilian children with CPP (171 girls, 16.8% familial cases). A large multiethnic group (1,599 subjects; Multiethnic Cohort, MEC) was used as control. DNA analysis and biochemical in vitro studies were performed. Results: A heterozygous LIN28B variant, p. H199R, was identified in a girl who developed CPP at 5.2 years. This variant was absent in 310 Brazilian control individuals, but it was found in the same allele frequency in women from the MEC cohort, independent of the age of menarche. Functional studies revealed that when ectopically expressed in cells, the mutant protein was capable of binding pre-let-7 microRNA and inhibiting let-7 expression to the same extent as wild-type Lin28B protein. Other rare LIN28B variants (p.P173P, c.198+32\_33delCT, g.9575731A>C and c.-11C>T) were identified in CPP patients and controls. Therefore, no functional mutation was identified. Conclusion: In vitro studies revealed that the rare LIN28B p.H199R variant identified in a girl with CPP does not affect the Lin28B function in the regulation of let-7 expression. Although LIN28B SNPs were associated with normal pubertal timing, rare variations in this gene do not seem to be commonly involved in the molecular pathogenesis of CPP. Copyright (C) 2012 S. Karger AG, Basel (AU)

• Processo FAPESP: 08/55953-4 - Análise dos genes Kiss1 e GPR54 em crianças com puberdade precoce dependente de gonadotrofina idiopática
• Beneficiário: Acácio Pinto da Silveira Neto
• Modalidade de apoio: Bolsas no Brasil - Mestrado