Truncating biallelic variant in DNAJA1, encoding the co-chaperone Hsp40, is associated with intellectual disability and seizures

Neurogenetics. 2019 May;20(2):109-115. doi: 10.1007/s10048-019-00573-6. Epub 2019 Apr 10.

Abstract

Intellectual disability poses a huge burden on the health care system, and it is one of the most common referral reasons to the genetic and child neurology clinic. Intellectual disability (ID) is genetically heterogeneous, and it is associated with several other neurological conditions. Exome sequencing is a robust genetic tool and has revolutionized the process of molecular diagnosis and novel gene discovery. Besides its diagnostic clinical value, novel gene discovery is prime in reverse genetics, when human mutations help to understand the function of a gene and may aid in better understanding of the human brain and nervous system. Using WES, we identified a biallelic truncating variant in DNAJA1 gene (c.511C>T p.(Gln171*) in a multiplex Saudi consanguineous family. The main phenotype shared between the siblings was intellectual disability and seizure disorder.

Keywords: Chaperone; Chaperonopathy; Co-chaperone; DNAJA1; Exome sequencing; Hsp40; Intellectual disability; Seizure disorder.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alleles*
  • Child
  • Consanguinity
  • Epilepsy / genetics*
  • Exome
  • Female
  • Genetic Variation*
  • HSP40 Heat-Shock Proteins / genetics*
  • Humans
  • Intellectual Disability / genetics*
  • Male
  • Molecular Chaperones / metabolism
  • Mutation
  • Pedigree
  • Phenotype
  • Saudi Arabia
  • Whole Exome Sequencing
  • Young Adult

Substances

  • DNAJA1 protein, human
  • DNAJB1 protein, human
  • HSP40 Heat-Shock Proteins
  • Molecular Chaperones