MARINA CUNHA SILVA PAZOLINI
Projetos de Pesquisa
Unidades Organizacionais
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina
5 resultados
Resultados de Busca
Agora exibindo 1 - 5 de 5
- High Frequency of MKRN3 Mutations in Male Central Precocious Puberty Previously Classified as Idiopathic(2017) BESSA, Danielle S.; MACEDO, Delanie B.; BRITO, Vinicius N.; FRANCA, Monica M.; MONTENEGRO, Luciana R.; CUNHA-SILVA, Marina; SILVEIRA, Leticia G.; HUMMEL, Tiago; BERGADA, Ignacio; BRASLAVSKY, Debora; ABREU, Ana Paula; DAUBER, Andrew; MENDONCA, Berenice B.; KAISER, Ursula B.; LATRONICO, Ana ClaudiaBackground/Aims: Recently, loss-of-function mutations in the MKRN3 gene have been implicated in the etiology of familial central precocious puberty (CPP) in both sexes. We aimed to analyze the frequency of MKRN3 mutations in boys with CPP and to compare the clinical and hormonal features of boys with and without MKRN3 mutations. Methods: This was a retrospective review of clinical, hormonal and genetic features of 20 male patients with idiopathic CPP evaluated at an academic medical center. The entire coding regions of MKRN3, KISS1 and KISS1R genes were sequenced. Results: We studied 20 boys from 17 families with CPP. All of them had normal brain magnetic resonance imaging. Eight boys from 5 families harbored four distinct heterozygous MKRN3 mutations predicted to be deleterious for protein function, p.Ala162Glyfs*14, p.Arg213Glyfs*73, p.Arg328Cys and p. Arg365Ser. One boy carried a previously described KISS1-activating mutation (p.Pro74Ser). The frequency of MKRN3 mutations among these boys with idiopathic CPP was significantly higher than previously reported female data (40 vs. 6.4%, respectively, p < 0.001). Boys with MKRN3 mutations had typical clinical and hormonal features of CPP. Notably, they had later pubertal onset than boys without MKRN3 abnormalities (median age 8.2 vs. 7.0 years, respectively, p = 0.033). Conclusion: We demonstrated a high frequency of MKRN3 mutations in boys with CPP, previously classified as idiopathic, suggesting the importance of genetic analysis in this group. The boys with CPP due to MKRN3 mutations had classical features of CPP, but with puberty initiation at a borderline age. (C) 2016 S. Karger AG, Basel
conferenceObject PATERNALLY INHERITED DLK1 DELETION AS A NOVEL CAUSE OF FAMILIAL CENTRAL PRECOCIOUS PUBERTY(2017) DAUBER, Andrew; CUNHA-SILVA, Marina; MACEDO, Delanie; BRITO, Vinicius; ABREU, Ana Paula; ROBERTS, Stephanie; MONTENEGRO, Luciana; ANDREW, Melissa; KRIBY, Andrew; WEIRAUCH, Matthew; LABILLOY, Guillaume; BESSA, Danielle; CARROLL, Rona; JACOBS, Dakota; CHAPPELL, Patrick; MENDONCA, Berenice B.; HAIG, David; KAISER, Ursula; LATRONICO, Ana Claudia- Paternally Inherited DLK1 Deletion Associated With Familial Central Precocious Puberty(2017) DAUBER, Andrew; CUNHA-SILVA, Marina; MACEDO, Delanie B.; BRITO, Vinicius N.; ABREU, Ana Paula; ROBERTS, Stephanie A.; MONTENEGRO, Luciana R.; ANDREW, Melissa; KIRBY, Andrew; WEIRAUCH, Matthew T.; LABILLOY, Guillaume; BESSA, Danielle S.; CARROLL, Rona S.; JACOBS, Dakota C.; CHAPPELL, Patrick E.; MENDONCA, Berenice B.; HAIG, David; KAISER, Ursula B.; LATRONICO, Ana ClaudiaContext: Central precocious puberty (CPP) results from premature activation of the hypothalamic-pituitary- gonadal axis. Few genetic causes of CPP have been identified, with the most common being mutations in the paternally expressed imprinted gene MKRN3. Objective: To identify the genetic etiology of CPP in a large multigenerational family. Design: Linkage analysis followed by whole-genome sequencing was performed in a family with five female members with nonsyndromic CPP. Detailed phenotyping was performed at the time of initial diagnosis and long-term follow-up, and circulating levels of Delta-like 1 homolog (DLK1) were measured in affected individuals. Expression of DLK1 was measured in mouse hypothalamus and in kisspeptin-secreting neuronal cell lines in vitro. Setting: Endocrine clinic of an academic medical center. Patients: Patients with familial CPP were studied. Results: A complex defect of DLK1 (similar to 14-kb deletion and 269-bp duplication) was identified in this family. This deletion included the 50 untranslated region and the first exon of DLK1, including the translational start site. Only family members who inherited the defect from their father have precocious puberty, consistent with the known imprinting of DLK1. The patients did not demonstrate additional features of the imprinted disorder Temple syndrome except for increased fat mass. Serum DLK1 levels were undetectable in all affected individuals. Dlk1 was expressed in mouse hypothalamus and in kisspeptin neuron-derived cell lines. Conclusion: We identified a genomic defect in DLK1 associated with isolated familial CPP. MKRN3 and DLK1 are both paternally expressed imprinted genes. These findings suggest a role of genomic imprinting in regulating the timing of human puberty.
conferenceObject ANTHROPOMETRIC, METABOLIC AND REPRODUCTIVE OUTCOME OF PATIENTS WITH CENTRAL PRECOCIOUS PUBERTY DUE TO HYPOTHALAMIC HAMARTOMA IN ADULT LIFE(2017) RAMOS, Carolina O.; LATRONICO, Ana Claudia; CUKIER, Priscila; MACEDO, Delanie; BESSA, Danielle S.; SILVA, Marina C.; ARNHOLD, Ivo J.; MENDONCA, Berenice B.; BRITO, Vinicius N.conferenceObject OUTCOMES OF GIRLS WITH IDIOPATHIC CENTRAL PRECOCIOUS PUBERTY TREATED WITH 1-AND 3-MONTH GONADOTROPIN-RELEASING HORMONE ANALOG FORMULATIONS(2017) RAMOS, Carolina O.; SILVA, Marina C.; SALLES, Priscila; MENDONCA, Berenice B.; LATRONICO, Ana Claudia; BRITO, Vinicius N.