Uniparental disomy as a cause of pediatric endocrine disorders

Uniparental disomy (UPD) refers to a condition in which two homologous chromosomes or chromosomal regions are inherited from one parent. Recent studies have shown that UPD is not rare among the general population, arising from trisomy rescue, gamete complementation, and other mechanisms. Although UPD is not necessarily pathogenic, it can lead to various disease phenotypes by causing imprinting disorders or by unmasking autosomal recessive mutations. Notably, known UPD-mediated autosomal recessive disorders include congenital adrenal hyperplasia due to 21-hydroxylase deficiency, 11β-hydroxylase deficiency, and 3β-hydroxysteroid dehydrogenase deficiency. In addition, UPD can occur in combination with additional cytogenetic abnormalities that may affect growth and development. Therefore, UPD represents a clinically important condition that accounts for a certain percentage of the etiology of growth failure and endocrine abnormalities. Although UPD is barely detectable by standard karyotyping or sequence analyses, it can be screened by single nucleotide polymorphism- and microsatellite-genotyping of patients and their parents, or by DNA methylation analysis of the patients. This mini-review introduces the underlying mechanisms and phenotypic consequences of UPD in association with pediatric endocrine disorders.