UNIPARENTAL DISOMY EXPLAINS THE OCCURRENCE OF THE ANGELMAN OR PRADER-WILLI-SYNDROME IN PATIENTS WITH AN ADDITIONAL SMALL INV DUP(15) CHROMOSOME

A patient with Angelman syndrome and a 46,XY/47,XY,+inv dup(15)(pter-- >q11: q11-->pter) karyotype and a patient with Prader-Willi syndrome a nd a 46,XY/47,XY,+inv dup(15)(pter-->q12: q12-->pter) karyotype were i nvestigated with molecular markers along chromosome 15. Paternal unipa rental isodisomy was found for all informative markers in the first ca se which indicates that this, rather than the presence of the extra ch romosome, is the cause of the Angelman syndrome phenotype. Similarly, the PWS patient showed maternal uniparental disomy with absence of PWS region material on the inv dup(15) chromosome. If (1) marker chromoso mes are an occasional by product of 'rescuing' a trisomic fertilisatio n, or (2) if duplication of the normal homologue in a zygote which has inherited a marker in place of the normal corresponding chromosome 'r escues' an aneuploid fertilisation, or (3) if the presence or formatio n of a marker chromosome increases the probability of non-disjunction, then uniparental disomy might be found occasionally in other subjects with de novo marker chromosomes.