A LARGE, DOMINANT PEDIGREE OF ATRIOVENTRICULAR SEPTAL-DEFECT (AVSD) -EXCLUSION FROM THE DOWN-SYNDROME CRITICAL REGION ON CHROMOSOME-21

We describe a large pedigree of individuals with autosomal dominant at rioventricular septal defect (AVSD). The pedigree includes affected in dividuals and individuals who have transmitted the defect but are not clinically affected. AVSDs are a rare congenital heart malformation th at occurs as only 2.8% of isolated cardiac lesions. They are the predo minant heart defect in children with Down syndrome, making chromosome 21 a candidate for genes involved in atrioventricular septal developme nt. We have carried out a linkage study in the pedigree by using 10 si mple-sequence polymorphisms from chromosome 21. Multipoint linkage ana lysis gives lod scores of less than -2 for the region of trisomy 21 as sociated with heart defects, which excludes a locus within this region as the cause of the defect in this family.