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.

Genetic Considerations in Recurrent Pregnancy Loss

“…The principle of anticipation in myotonic dystrophy and related diseases describes the worsening of symptom severity and earlier age of onset as the disease is passed to subsequent generations. For myotonic dystrophy, analysis of tissues from stillborn babies has shown the highest number of CTG repeats when compared with living carriers (Kotzot 1999).…”

Maternal uniparental isodisomy 20 in a foetus with trisomy 20 mosaicism: clinical, cytogenetic and molecular analysis

“…8 Infants with a normal karyotype from a pregnancy in which a mosaic trisomy cell line was found in amniocytes or trophoblastic cells, are potentially at risk for uniparental disomy (UPD). 9 There are five reports in the literature of UPD20 (one of which was confined to 20q) and abnormal phenotypic findings (Table 1). 10 -14 Here we describe a baby who was born without gross malformations following prenatal diagnosis of trisomy 20 mosaicism in amniocytes, which was confirmed in urine sediment and blood cells of the newborn, and where maternal uniparental isodisomy for chromosome 20 was detected in the diploid blood cells.…”

A novel automated strategy for screening cryptic telomeric rearrangements in children with idiopathic mental retardation

“…On the other hand, maternal isodisomy for chromosome 17 has previously been described in a 2-year-old boy with normal growth and psychomotor development, 19 and the terminal long arm of chromosome 17 is not known to undergo imprinting. 20 Further investigations are therefore required to know whether this region contains one or several imprinted gene(s).…”