Novel CLN3 mutation causing autophagic vacuolar myopathy

Neurology. 2014 Jun 10;82(23):2072-6. doi: 10.1212/WNL.0000000000000490. Epub 2014 May 14.


Objective: To identify the genetic cause of a complex syndrome characterized by autophagic vacuolar myopathy (AVM), hypertrophic cardiomyopathy, pigmentary retinal degeneration, and epilepsy.

Methods: Clinical, pathologic, and genetic study.

Results: Two brothers presented with visual failure, seizures, and prominent cardiac involvement, but only mild cognitive impairment and no motor deterioration after 40 years of disease duration. Muscle biopsy revealed the presence of widespread alterations suggestive of AVM with autophagic vacuoles with sarcolemmal features. Through combined homozygosity mapping and exome sequencing, we identified a novel p.Gly165Glu mutation in CLN3.

Conclusions: This study expands the clinical phenotype of CLN3 disease. Genetic testing for CLN3 should be considered in AVM with autophagic vacuoles with sarcolemmal features.

Publication types

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

MeSH terms

  • Adult
  • Autophagy / genetics
  • Cardiomyopathy, Hypertrophic / genetics*
  • Cardiomyopathy, Hypertrophic / pathology*
  • Cognitive Dysfunction / genetics
  • Cognitive Dysfunction / pathology*
  • Epilepsy / genetics
  • Epilepsy / pathology
  • Humans
  • Male
  • Membrane Glycoproteins / genetics*
  • Middle Aged
  • Molecular Chaperones / genetics*
  • Mutation
  • Retinitis Pigmentosa / genetics
  • Retinitis Pigmentosa / pathology
  • Vacuoles / genetics
  • Vacuoles / pathology


  • CLN3 protein, human
  • Membrane Glycoproteins
  • Molecular Chaperones