Bain type of X-linked syndromic mental retardation in a male with a pathogenic variant in HNRNPH2

Am J Med Genet A. 2020 Jan;182(1):183-188. doi: 10.1002/ajmg.a.61388. Epub 2019 Oct 31.

Abstract

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are RNA binding proteins, which aid in maturation, stabilization, and transport of mRNA. They have a significant role in cellular nucleic acid metabolism. The hnRNPs alter gene expression and are linked to various neurodegenerative disorders and cancers. Previously, six unrelated girls with developmental delay, intellectual disability, and hypotonia were found to have de novo heterozygous pathogenic missense variants in HNRNPH2, located on the X chromosome. A gain-of-function effect was proposed for the variant and it was thought to be lethal in males as no surviving males were identified. We describe a family with two affected siblings, one male and one female, with a known pathogenic variant in HNRNPH2, possibly due to maternal germline mosaicism.

Keywords: HNRNPH2; X-linked dominant; developmental delay; heterogeneous nuclear ribonucleoproteins; hypotonia; intellectual disability.

Publication types

  • Case Reports

MeSH terms

  • Child
  • Child, Preschool
  • Developmental Disabilities / genetics*
  • Developmental Disabilities / pathology
  • Female
  • Genetic Predisposition to Disease*
  • Heterogeneous-Nuclear Ribonucleoprotein Group F-H / genetics*
  • Humans
  • Intellectual Disability / genetics
  • Intellectual Disability / physiopathology
  • Male
  • Mental Retardation, X-Linked / diagnosis
  • Mental Retardation, X-Linked / genetics*
  • Mental Retardation, X-Linked / physiopathology
  • Muscle Hypotonia / genetics
  • Muscle Hypotonia / pathology
  • Mutation, Missense / genetics
  • Pedigree
  • Phenotype

Substances

  • HNRNPH2 protein, human
  • Heterogeneous-Nuclear Ribonucleoprotein Group F-H