Delineation of the critical deletion region for congenital heart defects, on chromosome 8p23.1

Deletions in the distal region of chromosome 8p (del8p) are associated with congenital heart malformations. Other major manifestations include microce phaly, intrauterine growth retardation, mental retardation, and a character istic hyperactive, impulsive behavior. We studied genotype-phenotype correl ations in nine unrelated patients with a de novo del8p, by using the combin ation of classic cytogenetics, FISH, and the analysis of polymorphic DNA ma rkers. With the exception of one large terminal deletion, all deletions wer e interstitial. In five patients, a commonly deleted region of similar to 6 Mb was present, with breakpoints clustering in the same regions. One patie nt without a heart defect or microcephaly but with mild mental retardation and characteristic behavior had a smaller deletion within this commonly del eted region. Two patients without a heart defect had a more proximal inters titial deletion that did not overlap with the commonly deleted region. Take n together, these data allowed us to define the critical deletion regions f or the major features of a del8p.