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Prospective evaluation of exome sequencing in the etiological investigation of syndromic short stature patients without clinical diagnosis

Grant number: 18/10893-6
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): May 01, 2019
Effective date (End): July 31, 2021
Field of knowledge:Biological Sciences - Genetics
Principal Investigator:Alexander Augusto de Lima Jorge
Grantee:Bruna Lucheze Freire
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:13/03236-5 - New approaches and methodologies in molecular-genetic studies of growth and pubertal development disorders, AP.TEM


The word syndrome is used to define a set of medical signs, symptoms and characteristics correlated with a particular condition. Short stature is one of the main features found in many known syndromes, and when it is associated with others signs such as, facial dimorphisms, NPMD and/or intellectual disabilities, major malformations (ex: cardiac defects, CNS malformation, renal agenesis, midline facial defects), we classify as a syndromic short stature, that is frequently result of a genetic defect. As a majority of the genetic syndromes related to the growth disorder are rare and/or phenotypically heterogeneous diseases, clinical diagnosis is a great challenge, making the molecular diagnosis important for therapeutic decision, in addition to genetic counseling of the family. The aim of this project is to study the molecular etiology of patients with syndromic short stature without a clinical diagnosis, through the exomic sequencing technology (n=50). In this way we hope to identify new genes responsible for syndromic short stature and to expand the phenotype associated to genes already implicated in syndromic short stature by describing atypical cases. Therefore, we intend to develop strategies for clinical investigation of these patients and to develop and implement a telemedicine platform for the evaluation of patients with syndromic growth disorder. We will use Agilent`s Sure Select system to prepare the exomes libraries. The bioinformatics analysis of the data will follow a flow previously established by the laboratory, and the variants found will be analyzed in relation to population frequency, position of the variant, in silico predisposition of pathogenicity, inheritance compatibility, biological plausibility, and subsequent segregation in relatives. (AU)