Classification of Uniparental Isodisomy Patterns That Cause Autosomal Recessive Disorders: Proposed Mechanisms of Different Proportions and Parental Origin in Each Pattern

Abstract

Patients with autosomal recessive (AR) disorders are usually born to parents both of whom are heterozygous carriers of the disease. However, in some instances only one of the parents is a carrier and a mutation is segregated to the patient through uniparental isodisomy (UPiD). Recently, an increasing number of such case reports has been published, and it has become clear that there are several different UPiD patterns that cause AR disorders. In this article, we report 3 remarkable patients with different patterns of UPiD. We then review 85 cases collected in the literature. We realized that they can be classified into 3 patterns: UPiD of the whole chromosome, segmental UPiD with uniparental heterodisomy (UPhD), and segmental UPiD caused by post-zygotic mitotic recombination (MiRe). Whole chromosomal UPiD accounted for the majority of cases, with paternal origin accounting for approximately twice as many cases as maternal origin. Most cases of segmental UPiD with UPhD were of maternal origin, with a dominancy of nondisjunction in meiosis I, while segmental UPiD through MiRe is the smallest pattern with equal parental origin. These differences in proportion and parental origin in each pattern can be explained by considering nondisjunction during oogenesis as the starting point and UPiD as subsequent events.