AB064. Autosomal recessive diseases caused by a rare mechanism: uniparental disomy

Abstract: Uniparental disomy (UPD) represents an imbalance in the distribution of paternal and maternal chromosomes in the offspring. It is defined as a condition in which both homologues of a chromosome are inherited from only one parent. UPD for some chromosomes does not exert any adverse effect on an individual. However, for certain chromosomes, it can result in abnormality through aberrant genomic imprinting, when the chromosomes contain imprinted genes. In isodisomy, not only is there a risk for a disturbance due to imprinting, but there is also risk that the two pairs of homologs are identical creating homozygosity for a large region of a certain chromosome, with an associated increased risk for recessive disorders. In this report, we will demonstrate two rare autosomal recessive diseases, argininosuccinic aciduria and recessive congenital methemoglobinemia, were caused by uniparental isodisomy or uniparental heterodisomy with segmental isodisomy. The molecular studies of this mechanism and literatures reviewed will be presented in this report.

Keywords: Uniparental disomy (UPD); recessive congenital methemoglobinemia; argininosuccinic aciduria; microsatellite genotyping