Novel case of neurodegeneration with brain iron accumulation 4 (NBIA4) caused by a pathogenic variant affecting splicing

Neurogenetics. 2018 Dec;19(4):257-260. doi: 10.1007/s10048-018-0558-4. Epub 2018 Nov 3.

Abstract

Neurodegeneration with brain iron accumulation type 4 (NBIA4) also known as MPAN (mitochondria protein-associated neurodegeneration) is a rare neurological disorder which main feature is brain iron accumulation most frequently in the globus pallidus and substantia nigra. Whole exome sequencing (WES) in a 12-year-old patient revealed 2 variants in the C19orf12 gene, a previously reported common 11 bp deletion c.204_214del11, p.(Gly69Argfs*10) and a novel splicing variant c.193+5G>A. Functional analysis of novel variant showed skipping of the second exon, resulting in a formation of a truncated nonfunctional protein. This is the first functionally annotated pathogenic splicing variant in NBIA4.

Keywords: C19orf12; Functional analysis; Iron accumulation; MPAN; NBIA; Neurodegeneration; Splicing.

Publication types

  • Case Reports

MeSH terms

  • Brain / diagnostic imaging
  • Brain / metabolism
  • Brain / pathology
  • Child
  • DNA Mutational Analysis
  • Female
  • Humans
  • Iron / metabolism
  • Iron Metabolism Disorders / genetics*
  • Magnetic Resonance Imaging
  • Mitochondrial Proteins / genetics*
  • Neuroaxonal Dystrophies / genetics*
  • Pedigree
  • Protein Isoforms / genetics
  • RNA Splicing / genetics*
  • Republic of Belarus

Substances

  • C19orf12 protein, human
  • Mitochondrial Proteins
  • Protein Isoforms
  • Iron

Supplementary concepts

  • Neurodegeneration with brain iron accumulation (NBIA)