Investigation of two cases of paternal disomy 13 suggests timing of isochromosome formation and mechanisms leading to uniparental disomy

Uniparental disomy (UPD) is the abnormal inheritance of two copies of a chr omosome from the same parent. Possible mechanisms for UPD include trisomy r escue, monosomy rescue, gametic complementation, and somatic recombination. Most of these mechanisms can involve rearranged chromosomes, particularly isochromosomes and Robertsonian translocations. Both maternal and paternal UPD have been reported for most of the acrocentric chromosomes. However, on ly UPD for chromosomes 14 and 15 show an apparent imprinting effect. Herein , we present two cases of paternal UPD 13 involving isochromosomes. Both ca ses were referred for UPD studies due to the formation of a de novo rea(13q 13q). Case 2 was complicated by the segregation of a familial rob(13q14q) o f maternal origin. Both propositi were phenotypically normal at the time of examination. Polymorphic marker analysis in Case 1 showed the distribution of alleles of markers along chromosome 13 to be complete isodisomy, consis tent with an isochromosome. This rearrangement could have occurred either m eiotically, without recombination, or mitotically. A likely mechanism for U PD in this case is monosomy rescue, through postzygotic formation of the is ochromosome. In Case 2 the distribution of proximal alleles indicated an is ochromosome, but recombination was evident. Thus, this isochromosome must h ave formed prior to or during meiosis I. A likely mechanism for UPD in this case is gametic complementation, since the mother carries a rob(13q14q) an d is at risk of producing aneuploid gametes. However, trisomy rescue of a t risomy 13 conceptus cannot be completely excluded. Given that both cases we re phenotypically normal, these data further support that paternal UPD 13 d oes not have an adverse phenotypic outcome and, thus, does not show an appa rent imprinting effect. (C) 1999 Wiley-Liss, Inc.