ERCC6 dysfunction presenting as progressive neurological decline with brain hypomyelination

Am J Med Genet A. 2014 Nov;164A(11):2892-900. doi: 10.1002/ajmg.a.36709. Epub 2014 Sep 22.

Abstract

Mutations in ERCC6 are associated with growth failure, intellectual disability, neurological dysfunction and deterioration, premature aging, and photosensitivity. We describe siblings with biallelic ERCC6 mutations (NM_000124.2:c. [543+4delA];[2008C>T]) and brain hypomyelination, microcephaly, cognitive decline, and skill regression but without photosensitivity or progeria. DNA repair assays on cultured skin fibroblasts confirmed a defect of transcription-coupled nucleotide excision repair and increased ultraviolet light sensitivity. This report expands the disease spectrum associated with ERCC6 mutations.

Keywords: Cockayne syndrome group B; deafness; developmental delay; hypomyelination; intellectual disability; vision loss.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Alternative Splicing
  • Biomarkers / metabolism
  • Brain / pathology*
  • Brain / physiopathology*
  • Child
  • Child, Preschool
  • DNA Helicases / genetics*
  • DNA Helicases / metabolism
  • DNA Mutational Analysis
  • DNA Repair Enzymes / genetics*
  • DNA Repair Enzymes / metabolism
  • Facies
  • Female
  • Gene Expression
  • Hereditary Central Nervous System Demyelinating Diseases / diagnosis
  • Hereditary Central Nervous System Demyelinating Diseases / genetics*
  • Humans
  • Introns
  • Magnetic Resonance Imaging
  • Male
  • Mutation
  • Nervous System Diseases / diagnosis
  • Nervous System Diseases / genetics*
  • Pedigree
  • Phenotype
  • Poly-ADP-Ribose Binding Proteins
  • Siblings

Substances

  • Biomarkers
  • Poly-ADP-Ribose Binding Proteins
  • DNA Helicases
  • ERCC6 protein, human
  • DNA Repair Enzymes