Absence of Functional LIN28B Mutations in a Large Cohort of Patients with Idiopathic Central Precocious Puberty
Open accessAbstract
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.
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Mutations in LIN28B have not been identified in patients with central precocious puberty or constitutional delay of growth and puberty.
“Mutations in LIN28B have not been identified in patients with central precocious puberty or constitutional delay of growth and puberty.86,87”
From Pubertal development and regulation (2016) · cites this paper as [87]
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- Authors
- Silveira-Neto, A. P., Leal, L. F., Emerman, A. B., Henderson, K. D., Piskounova, E., Henderson, B. E., Gregory, R. I., Silveira, L. F. G., Hirschhorn, J. N., Nguyen, T. T., Beneduzzi, D., Tusset, C., Reis, A. C. S., Brito, V. N., Mendonca, B. B., Palmert, M. R., Antonini, S. R., & Latronico, A. C.
- Affiliations
- Universidade de São Paulo (BR)
- Boston Children's Hospital (US)
- City Of Hope National Medical Center (US)
- University of Southern California (US)
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (BR)
- University of Toronto (CA)
- ORCID
- Venue
- Hormone Research in Paediatrics
- Publisher
- S. Karger AG
- Published
- 2012
- Volume
- 78
- Issue
- 3
- Pages
- 144-150
- ISSN
- 1663-2818 (ISSN-L)
- 1663-2826
- PMC
- PMC3526815
- OpenAlex
- W1986014733
- Cited by
- 34
- References
- 29
- Citations by year
- 2025: 1 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 5 · 2018: 3 · 2017: 2 · 2016: 4 · 2015: 6 · 2014: 4 · 2013: 2
- FWCI
- 4.47
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Hormone Research in Paediatrics (publishedVersion)
- PubMed (publishedVersion)
- Scientific Electronic Library Online (São Paulo Research Foundation, Latin American and Caribbean Center on Health Sciences Information, Conselho Nacional de Desenvolvimento Científico e Tecnológico) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- National Institute of General Medical Sciences (R01GM086386)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD048960)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Keywords
- LIN28B, idiopathic central precocious puberty, let-7 microRNA, pubertal timing, rare variants, genetic pathogenesis
- MeSH terms
- Adolescent, Adult, Child, Child, Preschool, DNA-Binding Proteins, Female, Gene Expression Regulation, HeLa Cells, Humans, Infant, Infant, Newborn, Male, Puberty, Precocious, Cohort Studies, RNA-Binding Proteins, Amino Acid Substitution, Mutation, Missense, MicroRNAs, HEK293 Cells
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