Hormone research in paediatrics · 2012
Absence of functional LIN28B mutations in a large cohort of patients with idiopathic central precocious puberty.
Клиническое исследованиеСтатьяМногоцентровое исследованиеПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Silveira-Neto Acácio P, Leal Leticia Ferro, Emerman Amy B, Henderson Katherine D, Piskounova Elena, Henderson Brian E, Gregory Richard I, Silveira Letícia F Gontijo, Hirschhorn Joel N, Nguyen Thutrang T, Beneduzzi Daiane, Tusset Cintia, Reis Ana Claudia S, Brito Vinicius N, Mendonca Berenice B, Palmert Mark R, Antonini Sonir R, Latronico Ana Claudia
Аннотация
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.
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.