DNAJC12-associated developmental delay, movement disorder, and mild hyperphenylalaninemia identified by whole-exome sequencing re-analysis

Eur J Hum Genet. 2018 Dec;26(12):1867-1870. doi: 10.1038/s41431-018-0237-9. Epub 2018 Aug 23.

Abstract

Hyperphenylalaninemia, movement disorder, and intellectual disability due to variants in DNAJC12 is a recently reported inherited neurotransmitter disorder. We report two new patients with this new genetic disorder. Patient 1 is a 6-year-11-month-old boy with mild hyperphenylalaninemia and global developmental delay (GDD). Seventeen-year-old male sibling of patient 1 had GDD from the first year of life. He had mild hyperphenylalaninemia at 11.5 years of age following his younger brother's diagnosis. He had low levels of homovanillic acid and 5-hydroxyindolacetic acid in the cerebrospinal fluid. Whole-exome sequencing (WES) was normal in 2016. After the first description of DNAJC12-associated hyperphenylalaninemia, dystonia, and intellectual disability in 2017, WES re-analysis identified a homozygous c.58_59delGG (p.(Gly20Metfs*2)) variant in DNAJC12. His younger brother was homozygous for the same variant, confirming the diagnosis of DNAJC12-associated hyperphenylalaninemia, movement disorder, and intellectual disability. Mild hyperphenylalaninemia and GDD should warrant targeted DNAJC12 genetic testing for the early diagnosis of DNAJC12-associated hyperphenylalaninemia, movement disorder, and intellectual disability.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Child
  • Developmental Disabilities / genetics*
  • Developmental Disabilities / pathology
  • Humans
  • Male
  • Movement Disorders / genetics*
  • Movement Disorders / pathology
  • Mutation
  • Phenylketonurias / genetics*
  • Phenylketonurias / pathology
  • Repressor Proteins / genetics*
  • Siblings

Substances

  • DNAJC12 protein, human
  • Repressor Proteins