Abnormal phenotypes in uniparental disomy (UPD): fundamental aspects and a critical review with bibliography of UPD other than 15

Abstract

Uniparental disomy (UPD) is the inheritance of both homologous chromosomes from only one parent. The bases are always two events, either two meiotic, or one meiotic and one mitotic, or two mitotic. An aberrant imprint, homozygosity of autosomal recessive gene mutations, homozygosity of X-chromosomal disorders in females, and father-to-son transmission of X-linked traits are the possible and yet repeatedly documented consequences sometimes associated with unfavorable handicaps. Fertilization of a disomic (=hyperhaploid) gamete by a gamete monosomic for the same chromosome and subsequent loss of the normally inherited chromosome (trisomy rescue) is the most frequently supposed mechanism of formation and might result in mosaicism in the placenta or even in a subset of fetal tissues. This low-level mosaicism can remain undetected and renders the delineation of a phenotype more difficult. Therefore, the phenotype of cases with UPD is determined by mosaicism, genomic imprinting, the nonmendelian inheritance of monogenic disorders, or by a combination of all these factors. A survey of all reported cases demonstrates a preponderance of maternal versus paternal UPD (approximately 3:1) and an unequal chromosomal distribution. Most likely, deleterious trisomy mosaicism, imprinted genes, the nature of the chromosome itself, the clinical interest in a single chromosome, and, last but not least, an ascertainment bias are therefore responsible.