A patient with a supernumerary marker chromosome (15), Angelman syndrome, and uniparental disomy resulting from paternal meiosis II non-disjunction.

The chromosome 15 region q11-q13 is imprinted and contains a number of genes that are expressed only from the paternally or the maternally inherited chromosome. This region is also prone to structural rearrangements including interstitial duplications and triplications, inversions, translocations, deletions, and the formation of supernumerary marker chromosomes (SMCs). 7 These rearrangements are associated with a wide range of abnormal phenotypes depending upon both the nature of the rearrangement and on the parental origin. For example, Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct neurobehavioural disorders that are both caused by a deletion of 15q11-q13. A deletion on the maternally inherited chromosome 15 gives rise to AS while a paternally inherited deletion causes PWS. These conditions can also be caused by uniparental disomy (UPD) of chromosome 15: maternal UPD cases will be functionally nullisomic for those genes expressed only from a paternally inherited chromosome and gives rise to PWS, while paternal UPD causes AS. Additional copies of the Prader-Willi/Angelman syndrome critical region (PWACR) have also been reported and can occur as familial cases or arise de novo. Unlike deletions, additional copies of the PWACR appear to be associated with an abnormal phenotype only when inherited maternally. 9 These additional copies can occur as interstitial duplications/ triplications or as SMC(15). SMC(15) is the most common marker chromosome observed in man, accounting for 50% of all cases. There are two basic types: large SMC(15) extend over most or all of the q11-q13 region, including the PWACR, and are associated with abnormal phenotypes ; small SMC(15) do not contain the PWACR and are not generally associated with an abnormal phenotype, 12 although they have occasionally been shown to occur in association with other disease causing abnormalities such as 15q11-q13 deletions and UPD(15). In all large and small de novo cases where the origin has been determined, the SMC(15) has been shown to be derived maternally. We report a boy with an abnormal phenotype and a de novo SMC(15). Molecular and molecular cytogenetic analysis showed that the SMC did not include the PWACR. This investigation fortuitously showed that the boy had inherited both chromosome 15 homologues from his father, indicating paternal UPD consistent with a diagnosis of AS. Interestingly, the UPD in this case is likely to have arisen because of paternal non-disjunction at meiosis II followed by trisomy rescue and is the first reported case of its kind.