Novel patterns of inheritance of genetic disease are illustrated by the Angelman syndrome.

Abstract

To characterise the molecular abnormalities present in a cohort of patients with the Angelman syndrome. DNA samples from 10 patients with the Angelman syndrome were investigated with molecular probes. Family studies were performed by means of DNA polymorphism analysis and densitometric estimation of allele copy number to determine the underlying mutation and its parental origin. Nine probands were shown to have molecular (DNA) deletions involving chromosome 15q11-q13. Polymorphism analyses demonstrated that all deletions were maternal in origin. Five of the nine had normal karyotypes, with deletions only detected after DNA study. One patient had inherited both chromosomes 15 from her father. This represented an example of paternal uniparental disomy of chromosome 15. Development of the Angelman syndrome can result from either deletion of the maternally-derived copy of chromosome 15q11-q13 or the presence of two paternally derived copies of chromosome 15, that is, uniparental disomy. DNA testing allows the identification of deletions that are not seen on cytogenetic analysis and can provide additional information regarding the parental origin of the deletion. Uniparental disomy is most readily established by DNA studies.