Deletions within chromosome 22q11 in familial congenital heart disease.

Because a locus on chromosome 22q11 is deleted in most individuals with DiGeorge and Shprintzen syndromes--conditions in which heart abnormalities are an important feature--we have looked for deletions in nine families with recurrent outflow-tract heart defects. In five families, chromosome 22 deletions were detected in all the living affected individuals studied and also in the clinically normal father of three affected children. The deletion was transmitted from parents to offspring and was associated with an increase in the severity of cardiac defects. No deletions were found in four families in which the parents were normal and affected siblings had anatomically identical defects. We propose that deletions within band q11 of chromosome 22 are an important cause of familial heart defects.