Whole exome sequencing revealed mutations in FBXL4, UNC80, and ADK in Thai patients with severe intellectual disabilities

Gene. 2019 May 15;696:21-27. doi: 10.1016/j.gene.2019.01.049. Epub 2019 Feb 14.

Abstract

Intellectual disabilities (ID) are etiologically heterogeneous. Advanced molecular techniques could be helpful in identification of the underlying genetic defects. We aimed to characterize clinical and molecular features of three Thai patients with ID. Patient 1 had ID, hypotonia and lactic acidosis. Patient 2 had ID and growth failure. Patient 3 had ID, seizure, diarrhea and hypoglycemia. Whole exome sequencing found that Patient 1 was homozygous for a nonsense, c.1303C>T (p.Arg435Ter), mutation in FBXL4, a gene responsible for encephalomyopathic mitochondrial DNA depletion syndrome-13 (MTDPS13). Patient 2 was compound heterozygous for two novel mutations, c.3226C>T (p.Arg1076Ter) and c.3205C>T (p.Arg1069Ter), in UNC80, a known gene of infantile hypotonia with psychomotor retardation and characteristic facies-2 (IHPRF2). Patient 3 was homozygous for a novel missense, c.427T>C (p.Cys143Arg), mutation in ADK, a known gene of adenosine kinase deficiency leading to hypermethioninemia. This study expands the mutational spectra of ID genes.

Keywords: ADK; FBXL4; Intellectual disability; UNC 80.

Publication types

  • Case Reports

MeSH terms

  • Adenosine Kinase / genetics*
  • Carrier Proteins / genetics*
  • F-Box Proteins / genetics*
  • Female
  • Genetic Testing / methods*
  • Homozygote
  • Humans
  • Infant
  • Intellectual Disability / diagnosis
  • Intellectual Disability / genetics*
  • Membrane Proteins / genetics*
  • Mutation
  • Severity of Illness Index
  • Thailand
  • Ubiquitin-Protein Ligases / genetics*
  • Whole Exome Sequencing

Substances

  • Carrier Proteins
  • F-Box Proteins
  • Membrane Proteins
  • Unc80 protein, human
  • Ubiquitin-Protein Ligases
  • Adenosine Kinase
  • FbxL4 protein, human