A DYNC1H1 mutation causes a dominant spinal muscular atrophy with lower extremity predominance

Neurogenetics. 2012 Nov;13(4):327-32. doi: 10.1007/s10048-012-0337-6. Epub 2012 Jul 31.


Whole-exome sequencing of two affected sibs and their mother who showed a unique quadriceps-dominant form of neurogenic muscular atrophy disclosed a heterozygous DYNC1H1 mutation [p.H306R (c.917A>G)]. The identical mutation was recently reported in a pedigree with the axonal form of Charcot-Marie-Tooth disease. Three other missense mutations in DYNC1H1 were also identified in families with dominant spinal muscular atrophy with lower extremity predominance. Their clinical features were consistent with those of our family. Our study has demonstrated that the same DYNC1H1 mutation could cause spinal muscular atrophy as well as distal neuropathy, indicating pleotropic effects of the mutation.

Publication types

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

MeSH terms

  • Adolescent
  • Base Sequence
  • Child
  • Cytoplasmic Dyneins / genetics*
  • Exome
  • Female
  • Genes, Dominant*
  • Humans
  • Lower Extremity Deformities, Congenital / diagnostic imaging
  • Lower Extremity Deformities, Congenital / genetics*
  • Lower Extremity Deformities, Congenital / pathology
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Muscle, Skeletal / diagnostic imaging
  • Muscle, Skeletal / pathology
  • Muscular Atrophy, Spinal / diagnostic imaging
  • Muscular Atrophy, Spinal / genetics*
  • Muscular Atrophy, Spinal / pathology
  • Mutation
  • Pedigree
  • Sequence Analysis, DNA
  • Tomography, X-Ray Computed


  • DYNC1H1 protein, human
  • Cytoplasmic Dyneins