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

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dc.contributor Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.author SILVEIRA-NETO, Acacio P. FMUSP-HC
LEAL, Leticia Ferro
EMERMAN, Amy B.
HENDERSON, Katherine D.
PISKOUNOVA, Elena
HENDERSON, Brian E.
GREGORY, Richard I.
SILVEIRA, Leticia F. Gontijo FMUSP-HC
HIRSCHHORN, Joel N.
NGUYEN, Thutrang T.
BENEDUZZI, Daiane FMUSP-HC
TUSSET, Cintia FMUSP-HC
REIS, Ana Claudia S.
BRITO, Vinicius N. FMUSP-HC
MENDONCA, Berenice B. FMUSP-HC
PALMERT, Mark R.
ANTONINI, Sonir R.
LATRONICO, Ana Claudia FMUSP-HC
dc.date.issued 2012
dc.identifier.citation HORMONE RESEARCH IN PAEDIATRICS, v.78, n.3, p.144-150, 2012
dc.identifier.issn 1663-2818
dc.identifier.uri http://observatorio.fm.usp.br/handle/OPI/437
dc.description.abstract 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.
dc.description.sponsorship · Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
· Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [05/04726, 08/55953-4]
· National Institute of General Medical Sciences (NIH-NIGMS)[1R01GM086386-01A1]
· Harvard Stem Cell Institute
· Emerald Foundation
· National Institutes of Health (NIH) [R01-HD048960]
dc.language.iso eng
dc.publisher KARGER
dc.relation.ispartof Hormone Research in Paediatrics
dc.rights restrictedAccess
dc.subject LIN28B gene; Central precocious puberty; Let-7 microRNA; Early menarche; Late menarche
dc.subject.other genome-wide association; caenorhabditis-elegans; menarche; age; metaanalysis; lin-28; loci; rna
dc.title Absence of Functional LIN28B Mutations in a Large Cohort of Patients with Idiopathic Central Precocious Puberty
dc.type article
dc.rights.holder Copyright KARGER
dc.description.group LIM/42
dc.identifier.doi 10.1159/000342212
dc.identifier.pmid 22964795
dc.type.category original article
dc.type.version publishedVersion
hcfmusp.author SILVEIRA-NETO, Acacio P.:FM:
hcfmusp.author SILVEIRA, Leticia F. Gontijo:HC:ICHC
hcfmusp.author BENEDUZZI, Daiane:FM:
hcfmusp.author TUSSET, Cintia:FM:
hcfmusp.author BRITO, Vinicius N.:HC:LIM/42
hcfmusp.author MENDONCA, Berenice B.:FM:MCM
hcfmusp.author LATRONICO, Ana Claudia:FM:MCM
hcfmusp.author.external · LEAL, Leticia Ferro:Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Puericultura & Pediat, Sao Paulo, Brazil
· EMERMAN, Amy B.:Harvard Univ, Sch Med,Childrens Hosp, Dept Biol Chem & Mol Pharmacol, Stem Cell Program, Cambridge, MA 02138 USA
· HENDERSON, Katherine D.:City Hope Natl Med Ctr, Dept Populat Sci, Duarte, CA 91010 USA
· PISKOUNOVA, Elena:Harvard Univ, Sch Med,Childrens Hosp, Dept Biol Chem & Mol Pharmacol, Stem Cell Program, Cambridge, MA 02138 USA
· HENDERSON, Brian E.:Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA
· GREGORY, Richard I.:Harvard Univ, Sch Med,Childrens Hosp, Dept Biol Chem & Mol Pharmacol, Stem Cell Program, Cambridge, MA 02138 USA
· HIRSCHHORN, Joel N.:Harvard Univ, Sch Med, Dept Genet, Cambridge, MA 02138 USA; Childrens Hosp Boston, Div Genet & Ctr Basic & Translat Obes Res, Boston, MA USA; Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA; Cambridge Ctr, Cambridge, MA USA
· NGUYEN, Thutrang T.:Childrens Hosp Boston, Div Genet & Ctr Basic & Translat Obes Res, Boston, MA USA; Cambridge Ctr, Cambridge, MA USA
· REIS, Ana Claudia S.:Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Puericultura & Pediat, Sao Paulo, Brazil
· PALMERT, Mark R.:Univ Toronto, Div Endocrinol, Toronto, ON, Canada; Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada
· ANTONINI, Sonir R.:Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Puericultura & Pediat, Sao Paulo, Brazil
hcfmusp.origem.id WOS:000310562400002
hcfmusp.origem.id 2-s2.0-84865854451
hcfmusp.publisher.city BASEL
hcfmusp.publisher.country SWITZERLAND
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dc.description.index MEDLINE
hcfmusp.citation.wos 19
hcfmusp.affiliation.country Brasil
hcfmusp.affiliation.country Estados Unidos
hcfmusp.affiliation.country Canadá


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