Investigative approach in cleft lip and palate and congenital cadiopathy related to 22q11.2 deletion syndrome using open array and aGH techniques

Abstract

Cleft lip and palate (CLP) occurs in 1:600 to 1000 births and most common form is isolated. The 22q11.2 Deletion Syndrome (22q11.2 Del S.) has a prevalence of 1:2.000 to 7.000 births and it is characterized by multiple anomalies, including cardiac anomalies and oral clefts. The present study aims to investigate: 1) association between 243 tagging SNPs in 38 candidate genes to isolated CLP based on a case-control study (total of 525 individuals), using the Open Array technique, 2) investigate the presence of copy number variations (CNVs) in patients with clinical suspicious of 22q11.2 Del S., confirm or not by laboratorial techniques, that presents cardiopathys related to it, using the array Genomic Hybridization (aGH) methodology by CytoScan HD chip, Affymetrix® (about 200 cases). This is a complementary study from previously projects of the same research group (FAPESP n.2008/50421-4, and 2009/08756-1, 2008/105960), using the information collected using the standardized protocol developed by the Clinical and Family Brazilian Database of Typical Orofacial Clefts (DB) and clinical protocol to investigate the 22q11.2 Del S. Control group consists of healthy subjects without CLP in three generations, whose DNA samples have been already stored. This research is justified for the following reasons: 1. Identification of the genetic contribution in the isolated CLP in Brazilian population through Open Array technique, 2. Description of the importance of CNVs and 22q11.2 deletion in the genesis of 22q11.2 Del S. and specific cardiac anomalies. If necessary, additional techniques will be used to confirm the results. Initially, data analysis will be descriptive. This study probably will suggest areas for further research, or will even detect new genes associated with cleft lip and palate and 22q11.2 Del S and cardiopathy. (AU)