Phenotype related with p.L142fsX161 STAT5B mutation in the heterozygous state

• Grant number: 10/19809-6
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2011
• End date: March 31, 2013
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Alexander Augusto de Lima Jorge
• Grantee: Alexander Augusto de Lima Jorge
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The growth hormone (GH) / insulin-like growth factor type 1 (IGF-1) system is the principal determinant and regulator of postnatal linear growth. The growth hormone insensitivity (GHI) is defined as the inability of target tissues to respond normally to GH action. IGH is mainly caused by mutations in the GH receptor gene (GHR, Laron Syndrome). In 2003, the first patient with IGH caused by homozygous inactivating mutation of STAT5B, a key molecule in signal transduction via GHR, was described. Over the past six years other families have been identified. These patients have clinical features similar to those observed in patients with Laron syndrome, but patients with STAT5b defects also have severe immunological dysfunction manifested as lymphoid interstitial pneumonia, viral infections exacerbated autoimmune events. Little information exists about such defects in heterozygous carriers. Therefore we intend to better characterize the anthropometric, hormonal and immunological effect of STAT5b mutation in the heterozygous state. This study is part of an international study group that evaluates all the families with mutations in STAT5B identified so far. The patients described by our group born from nonconsanguineous parents of normal stature. They live in a Brazilian south city called Criciuma. As a secondary objective, we intend to evaluate the presence of the mutation of STAT5B in a large group of healthy local controls to assess the frequency of this allele in the population. To analyze the effect of the mutation of STAT5B p.L142fsX161 will trace the heterozygous mutation identified in the maternal and paternal relatives of the index case of family recent described. Comparison of phenotype will be held between individuals heterozygous for the mutation and homozygous for the wild type allele in the same family. These families are characterized according to the anthropometric, hormonal and immune systems. To assess the prevalence of the mutation of STAT5B p.L142fsX161 population of Criciuma, we will collect DNA sample of 1000 unrelated healthy individuals and natural inhabitants of this city. (AU)

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)

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, SEP 2015. (10/19809-6, 13/03236-5, 11/15078-0)

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, 2017-06-05. (10/19809-6, 16/03318-0, 11/15078-0)