First missense mutation outside of SERAC1 lipase domain affecting intracellular cholesterol trafficking

Neurogenetics. 2016 Jan;17(1):51-6. doi: 10.1007/s10048-015-0463-z. Epub 2015 Oct 7.

Abstract

We report the clinical and genetic findings in a Spanish boy who presented MEGDEL syndrome, a very rare inborn error of metabolism. Whole-exome sequencing uncovered a new homozygous mutation in the serine active site containing 1 (SERAC1) gene, which is essential for both mitochondrial function and intracellular cholesterol trafficking. Functional studies in patient fibroblasts showed that p.D224G mutation affects the intracellular cholesterol trafficking. Only three missense mutations in this gene have been described before, being p.D224G the first missense mutation outside of the SERAC1 serine-lipase domain. Therefore, we conclude that the defect in cholesterol trafficking is not limited to alterations in this specific part of the protein.

Keywords: Cholesterol; MEGDEL syndrome; Mitochondria; SERAC1; WES; mtDNA.

Publication types

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

MeSH terms

  • Biological Transport / genetics
  • Brain Diseases, Metabolic, Inborn / genetics
  • Brain Diseases, Metabolic, Inborn / metabolism
  • Carboxylic Ester Hydrolases / chemistry
  • Carboxylic Ester Hydrolases / genetics*
  • Catalytic Domain / genetics
  • Child
  • Cholesterol / metabolism*
  • Consanguinity
  • Humans
  • Intracellular Space / metabolism
  • Lipase / chemistry
  • Lipid Metabolism, Inborn Errors / genetics*
  • Lipid Metabolism, Inborn Errors / metabolism
  • Male
  • Mutation, Missense*
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / metabolism
  • Protein Structure, Tertiary / genetics

Substances

  • Cholesterol
  • Carboxylic Ester Hydrolases
  • SERAC1 protein, human
  • Lipase