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Search for mutations in C-type natriuretic peptide receptor gene (NPR2) in individuals with idiopathic short stature

Grant number: 11/11801-9
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): December 01, 2011
Effective date (End): November 30, 2015
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Alexander Augusto de Lima Jorge
Grantee:Gabriela de Andrade Vasques
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Longitudinal bone growth occurs at the growth plate by endochondral ossification. This process, that involves chondrocytes proliferation and differentiation and extracellular matrix secretion, is regulated by many hormonal and local factors. Over the past several years, C-type natriuretic peptide (CNP) and its receptor (NPR-B) system has emerged as an important regulator of endochondral bone growth. Animal models showed its role in increasing the proliferation and differentiation of chondrocytes and in producing cartilage matrix. Homozygous mutations in NPR-B gene (NPR2) cause acromesomelic dysplasia, type Maroteaux, an autossomal recessive skeletal dysplasia with extreme short stature. Data from NPR2 mutation carriers showed they were shorter than population-matched controls, and it has been suggested that heterozygous mutations in NPR2 could be a cause of idiopathic short stature (ISS). We will study 100 patients with ISS to test this hypothesis. The number of patients is enough (statistical power 90%) to identify NPR2 mutations if they occur with a frequency greater than or equal to 1.5% in the population with ISS. DNA will be extracted from peripheral leukocytes, all 22 exons of NPR2 will be amplified by PCR with intronic primers and amplimers will be directly sequenced. Our findings will be correlated with phenotype of family members and analyzed in controls with normal height. (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)
VASQUES, GABRIELA A.; ARNHOLD, IVO J. P.; JORGE, ALEXANDER A. L. Role of the Natriuretic Peptide System in Normal Growth and Growth Disorders. Hormone Research in Paediatrics, v. 82, n. 4, p. 222-229, 2014. Web of Science Citations: 23.
VASQUES, GABRIELA A.; AMANO, NAOKO; DOCKO, ANA J.; FUNARI, MARIANA F. A.; QUEDAS, ELISANGELA P. S.; NISHI, MIRIAN Y.; ARNHOLD, IVO J. P.; HASEGAWA, TOMONOBU; JORGE, ALEXANDER A. L. Heterozygous Mutations in Natriuretic Peptide Receptor-B (NPR2) Gene as a Cause of Short Stature in Patients Initially Classified as Idiopathic Short Stature. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, v. 98, n. 10, p. E1636-E1644, OCT 2013. Web of Science Citations: 46.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
VASQUES, Gabriela de Andrade. Heterozygous mutations in natriuretic peptide receptor-B gene (NPR2) are cause of short stature initially classified as idiopathic. 2015. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina São Paulo.

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