A Japanese case of cerebellar ataxia, spastic paraparesis and deep sensory impairment associated with a novel homozygous TTC19 mutation

J Hum Genet. 2015 Apr;60(4):187-91. doi: 10.1038/jhg.2015.7. Epub 2015 Feb 5.

Abstract

Mitochondrial complex III (CIII) deficiency comprises a group of complex and heterogeneous genetic disorders. TTC19 mutations constitute a rare cause of CIII deficiency and are associated with neurological disorders in childhood and adulthood. Herein, we describe a 27-year-old Japanese man with cerebellar ataxia, spastic paraparesis, loss of deep sensation, mild frontal lobe dysfunction and transient psychiatric symptoms. Brain magnetic resonance imaging showed cerebellar atrophy and bilateral high-intensity signals in the inferior olives and regions adjacent to periaqueductal gray matter, on T2-weighted images. On whole-exome sequencing, we detected a novel homozygous frameshift mutation c.157_158dup [p.Pro54Alafs*48] in TTC19. Mitochondrial enzyme assays confirmed mild impairment of CIII enzymatic activity in lymphoblasts, which was consistent with TTC19-related CIII deficiency. His symptoms and radiological findings demonstrated an early stage or mild form of this disease, and further clarify the characteristics of patients with rare TTC19 mutations.

Publication types

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

MeSH terms

  • Adult
  • Asian People / genetics*
  • Brain / pathology
  • Cerebellar Ataxia / diagnosis
  • Cerebellar Ataxia / genetics*
  • DNA Mutational Analysis
  • Electron Transport Chain Complex Proteins / metabolism
  • Electron Transport Complex III / deficiency
  • Electron Transport Complex III / genetics
  • Homozygote*
  • Humans
  • Japan
  • Magnetic Resonance Imaging
  • Male
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Mitochondrial Diseases / diagnosis
  • Mitochondrial Diseases / genetics
  • Mitochondrial Proteins / genetics*
  • Mitochondrial Proteins / metabolism
  • Mutation*
  • Paraparesis, Spastic / diagnosis
  • Paraparesis, Spastic / genetics*
  • Perceptual Disorders / diagnosis
  • Perceptual Disorders / genetics*

Substances

  • Electron Transport Chain Complex Proteins
  • Membrane Proteins
  • Mitochondrial Proteins
  • TTC19 protein, human
  • Electron Transport Complex III

Supplementary concepts

  • Mitochondrial Complex III Deficiency