title: Association of tetralogy of Fallot with a distinct region of del22q11.2.
abstract: Congenital heart defects (CHDs) appear in greater frequency among relatives of patients and in individuals with DiGeorge syndrome (DGS) or velo-cardio-facial syndrome (VCFS). A majority of these patients and part of the apparently nonsyndromic CHD patients with conotruncal defects manifest hemizygous deletions within chromosome 22q11.2 (del22q11). We tested myocardial tissues of 31 CHD patients, 21 with tetralogy of Fallot (TOF) and 10 with a double-chamber right ventricle (DCRV). DNA isolated from tissues removed at corrective surgery was analyzed for homo- or heterozygosity of nine polymorphic short tandem repeat (STR) markers along the 22q11.2 region. DNA from the blood of 45 healthy individuals represented the general population. Ten of the 21 TOF patients (48%) showed homozygosity for three or more consecutive markers, indicating deletions of various sizes. No such indication was found for DCRV patients. Heterozygosity for markers D22S1648, D22S941, and D22S944 was lower in the TOF group than in normal controls, defining a minimal critical region (MCR) for the deletion. Our findings support an association between TOF and hemizygosity in 22q11.2, suggesting a distinct region, between markers D22S1638 and COMT, that may harbor TOF susceptibility genes.
authors.affiliation: Basil and Gerald Felsenstein Medical Research Center, Tel Aviv University, Tel Aviv, Israel. icekson@post.tau.ac.il
authors.forename: Gania
authors.initials: G
authors.lastname: Kessler-Icekson
authors.forename: Einat
authors.initials: E
authors.lastname: Birk
authors.forename: Ari Y
authors.initials: AY
authors.lastname: Weintraub
authors.forename: Yael
authors.initials: Y
authors.lastname: Barhum
authors.forename: Violetta
authors.initials: V
authors.lastname: Kotlyar
authors.forename: Hadassa
authors.initials: H
authors.lastname: Schlesinger
authors.forename: Rivka
authors.initials: R
authors.lastname: Rockah
authors.forename: Bernardo A
authors.initials: BA
authors.lastname: Vidne
authors.forename: Amos
authors.initials: A
authors.lastname: Frisch
mesh_terms: D000328:Adult; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006330:Heart Defects, Congenital / Q000235:genetics; D006352:Heart Ventricles / Q000002:abnormalities; D006801:Humans; D007223:Infant; D007557:Israel; D008297:Male; D011110:Polymorphism, Genetic; D020080:Tandem Repeat Sequences; D013771:Tetralogy of Fallot / Q000209:etiology / Q000235:genetics*