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Study of the phenotype associated to heterozigous STAT5B mutation p.L142fsX161

Grant number: 11/15078-0
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): February 01, 2012
Effective date (End): September 30, 2015
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal researcher:Alexander Augusto de Lima Jorge
Grantee:Renata da Cunha Scalco Tirapeli
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil


The growth hormone (GH) / insulin-like growth factor type 1 (IGF-1) axis is the main determinant and regulator of post-natal linear growth. Growth hormone insensibility (GHI) is defined as target tissues inability to respond normally to GH action and it is one of the classically described defects in the GH/IGF-1 axis. GHI is caused mainly by mutations in the GH receptor gene (GHR). In 2003 it was described the first patient with GHI caused by a homozygous inactivating mutation in STAT5B, a key molecule in GHR signal transduction. In the last years seven other families were described and among them one from Criciúma - Santa Catarina, described by our group in 2010. Besides clinical characteristics similar to patients with Laron syndrome, patients with homozygous STAT5B defects also present severe immune dysfunction, manifested as lymphocytic interstitial pneumonitis, exacerbated viral infections and other auto-immune events. There are still few data about these defects in heterozygosis, so we intend to better characterize the effect of the presence of one mutated allele in STAT5B gene regarding the anthropometric and hormonal features. As a secondary objective, we intend to screen the presence of the STAT5B mutation p.L142fsX161, described in the patients from Criciúma, in an extensive normal control group from this city, to estimate the frequency of this allele in the local population. To analyze the effect of this mutation in heterozygosis we will screen it in maternal and paternal relatives of the patients, who will be characterized in relation to anthropometric and hormonal parameters. Heterozygous individuals will be compared with individuals who are homozygous for the wild type allele in the same family. To evaluate the prevalence of STAT5B p.L142fsX161 mutation in the population of Criciúma, we will collect DNA samples from 1080 healthy subjects, not related to the family above mentioned, who were born and who live in this city. This amount of people will allow us to evaluate the presence of this allele in a frequency of 0.25% in this population with a statistical power of 99%. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
RENATA C. SCALCO; FERNANDA T. GONÇALVES; HADASSA C. SANTOS; MARI M. S. G. CARDENA; CARLOS A. TONELLI; MARIANA F. A. FUNARI; ROSANA M. ARACAVA; ALEXANDRE C. PEREIRA; CINTIA FRIDMAN; ALEXANDER A. L. JORGE. Growth hormone insensitivity with immune dysfunction caused by a STAT5B mutation in the south of Brazil: evidence for a founder effect. GENETICS AND MOLECULAR BIOLOGY, v. 40, n. 2, p. 436-441, . (11/15078-0, 16/03318-0, 10/19809-6)
SCALCO, RENATA C.; HWA, VIVIAN; DOMENE, HORACIO M.; JASPER, HECTOR G.; BELGOROSKY, ALICIA; MARINO, ROXANA; PEREIRA, ALBERTO M.; TONELLI, CARLOS A.; WIT, JAN M.; ROSENFELD, RON G.; et al. STAT5B mutations in heterozygous state have negative impact on height: another clue in human stature heritability. EUROPEAN JOURNAL OF ENDOCRINOLOGY, v. 173, n. 3, p. 291-296, . (10/19809-6, 13/03236-5, 11/15078-0)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
TIRAPELI, Renata da Cunha Scalco. Study of STAT5B mutation in Criciúma - Santa Catarina: frequency and phenotypic characterization of heterozygous individuals. 2015. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.

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