CINTIA TUSSET
Projetos de Pesquisa
Unidades Organizacionais
2 resultados
Resultados de Busca
Agora exibindo 1 - 2 de 2
- Mutational analysis of TAC3 and TACR3 genes in patients with idiopathic central pubertal disorders(2012) TUSSET, Cintia; NOEL, Sekoni D.; TRARBACH, Ericka B.; SILVEIRA, Leticia F. G.; JORGE, Alexander A. L.; BRITO, Vinicius N.; CUKIER, Priscila; SEMINARA, Stephanie B.; MENDONCA, Berenice B. de; KAISER, Ursula B.; LATRONICO, Ana ClaudiaObjective: To investigate the presence of variants in the TAC3 and TACR3 genes, which encode NKB and its receptor (NK3R), respectively, in a large cohort of patients with idiopathic central pubertal disorders. Subjects and methods: Two hundred and thirty seven patients were studied: 114 with central precocious puberty (CPP), 73 with normosmic isolated hypogonadotropic hypogonadism (IHH), and 50 with constitutional delay of growth and puberty (CDGP). The control group consisted of 150 Brazilian individuals with normal pubertal development. Genomic DNA was extracted from peripheral blood and the entire coding region of both TAC3 and TACR3 genes were amplified and automatically sequenced. Results: We identified one variant (p.A63P) in NKB and four variants, p.G18D, p.L58L (c.172C > T), p.W275* and p.A449S in NK3R, which were absent in the control group. The p.A63P variant was identified in a girl with CPP, and p.A449S in a girl with CDGP. The known p.G18D, p.L58L, and p.W275* variants were identified in three unrelated males with normosmic IHH. Conclusion: Rare variants in the TAC3 and TACR3 genes were identified in patients with central pubertal disorders. Loss-of-function variants of TACR3 were associated with the normosmic IHH phenotype.
- Absence of Functional LIN28B Mutations in a Large Cohort of Patients with Idiopathic Central Precocious Puberty(2012) SILVEIRA-NETO, Acacio P.; LEAL, Leticia Ferro; EMERMAN, Amy B.; HENDERSON, Katherine D.; PISKOUNOVA, Elena; HENDERSON, Brian E.; GREGORY, Richard I.; SILVEIRA, Leticia 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 ClaudiaAim: 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.