2 PEDIGREES OF AUTOSOMAL-DOMINANT ATRIOVENTRICULAR-CANAL DEFECT (AVCD) - EXCLUSION FROM THE CRITICAL REGION ON 8P

Atrioventricular canal defects (AVCD) constitute the predominant conge nital heart defect in Down syndrome. For this reason, a candidate gene involved in atrioventricular canal development was previously searche d and excluded in dominant pedigrees of AVCD, using linkage analysis o f polymorphisms from chromosome 21. Because of the striking associatio n between 8p deletion and AVCD, a search for an AVCD gene was carried out in two pedigrees of individuals with autosomal dominant AVCD using a set of DNA markers of the 8pter-->q12 region. These two families in clude affected individuals and subjects who have transmitted the defec t but are not clinically affected. Two-point lod scores were significa ntly negative for all markers at penetrance levels of 90% and 50%. Mul tipoint analysis excluded the region covered by the markers LPL-D8S262 and 30 cM to either side of this area. This result corroborates heter ogeneity of this heart defect and indicates that the genetic basis of familial AVCD is different from AVCD associated to either trisomy 21 o r 8p deletion. (C) 1995 Wiley-Liss, Inc.