Novel recessive mutations in MSTO1 cause cerebellar atrophy with pigmentary retinopathy

J Hum Genet. 2018 Mar;63(3):263-270. doi: 10.1038/s10038-017-0405-8. Epub 2018 Jan 16.

Abstract

Misato 1, mitochondrial distribution and morphology regulator (encoded by the MSTO1 gene), is involved in mitochondrial distribution and morphology. Recently, MSTO1 mutations have been shown to cause clinical manifestations suggestive of mitochondrial dysfunction, such as muscle weakness, short stature, motor developmental delay, and cerebellar atrophy. Both autosomal dominant and recessive modes of inheritance have been suggested. We performed whole-exome sequencing in two unrelated patients showing cerebellar atrophy, intellectual disability, and pigmentary retinopathy. Three novel mutations were identified: c.836 G > A (p.Arg279His), c.1099-1 G > A (p.Val367Trpfs*2), and c.79 C > T (p.Gln27*). Both patients had compound heterozygous mutations with a combination of protein-truncation mutation and missense mutation, the latter shared by them both. This survey of two patients with recessive and novel MSTO1 mutations provides additional clinical and genetic information on the pathogenicity of MSTO1 in humans.

MeSH terms

  • Adolescent
  • Age of Onset
  • Alleles
  • Atrophy
  • Cell Cycle Proteins / genetics*
  • Cell Line
  • Cerebellar Diseases / diagnosis*
  • Cerebellar Diseases / genetics*
  • Child
  • Child, Preschool
  • Cytoskeletal Proteins / genetics*
  • DNA Mutational Analysis
  • Female
  • Genes, Recessive*
  • Genotype
  • Humans
  • Infant
  • Magnetic Resonance Imaging
  • Male
  • Mutation*
  • Pedigree
  • Phenotype
  • Retinitis Pigmentosa / diagnosis*
  • Retinitis Pigmentosa / genetics*
  • Whole Genome Sequencing

Substances

  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • MSTO1 protein, human