Uniparental Isodisomy of Chromosome 1 Unmasking an Autosomal Recessive 3-Beta Hydroxysteroid Dehydrogenase Type II-Related Congenital Adrenal Hyperplasia

J Clin Res Pediatr Endocrinol. 2017 Mar 1;9(1):70-73. doi: 10.4274/jcrpe.3680. Epub 2016 Oct 31.

Abstract

Steroid 3-beta hydroxysteroid dehydrogenase type II (3β-HSD2) deficiency is a rare autosomal recessive form of congenital adrenal hyperplasia (CAH). We report the genetic basis of 3β-HSD2 deficiency arising from uniparental isodisomy (UPD) of chromosome 1. We describe a term undervirilized male whose newborn screen indicated borderline CAH. The patient presented on the 7th day of life in salt-wasting adrenal crisis. Steroid hormone testing revealed a complex pattern suggestive of 3β-HSD deficiency. Chromosomal microarray and single nucleotide polymorphism analysis revealed complete UPD of chromosome 1. Sanger sequencing of HSD3B2 revealed a previously described missense mutation, c.424G>A (p.E142K) in homozygous state, thus confirming the diagnosis of 3β-HSD2 deficiency. We provide evidence of the existence of an uncommon mechanism for HSD3B2 gene-related CAH arising from UPD of chromosome 1.

Publication types

  • Case Reports

MeSH terms

  • Adrenal Hyperplasia, Congenital / enzymology
  • Adrenal Hyperplasia, Congenital / genetics*
  • Chromosomes, Human, Pair 1 / genetics*
  • DNA Mutational Analysis
  • Genes, Recessive*
  • Homozygote
  • Humans
  • In Situ Hybridization, Fluorescence
  • Infant, Newborn
  • Male
  • Mutation, Missense
  • Progesterone Reductase / deficiency
  • Progesterone Reductase / genetics*
  • Uniparental Disomy*

Substances

  • 3 beta-hydroxysteroid dehydrogenase type II
  • Progesterone Reductase