First molecular study in Lebanese patients with Cockayne syndrome and report of a novel mutation in ERCC8 gene

BMC Med Genet. 2018 Sep 10;19(1):161. doi: 10.1186/s12881-018-0677-7.

Abstract

Background: Cockayne Syndrome (CS) is a rare autosomal recessive disorder characterized by neurological and sensorial impairment, dwarfism, microcephaly and photosensitivity. CS is caused by mutations in ERCC6 (CSB) or ERCC8 (CSA) genes.

Methods: Three patients with CS were referred to the Medical Genetics Unit of Saint Joseph University. Sanger sequencing of both ERCC8 and ERCC6 genes was performed: ERCC8 was tested in all patients while ERCC6 in one of them.

Results: Sequencing led to the identification of three homozygous mutations, two in ERCC8 (p.Y322* and c.843 + 1G > C) and one in ERCC6 (p.R670W). All mutations were previously reported as pathogenic except for the c.843 + 1G > C splice site mutation in ERCC8 which is novel.

Conclusions: Molecular diagnosis was established in all patients included in our study. A genotype-phenotype correlation is discussed and a link, between mutations and some specific religious communities in Lebanon, is suggested.

Keywords: CS; Cockayne; ERCC6; ERCC8; Lebanon; Sanger sequencing.

MeSH terms

  • Adolescent
  • Base Sequence
  • Child, Preschool
  • Cockayne Syndrome / diagnosis
  • Cockayne Syndrome / genetics*
  • Cockayne Syndrome / pathology
  • DNA Helicases / genetics*
  • DNA Mutational Analysis
  • DNA Repair Enzymes / genetics*
  • Exons
  • Female
  • Gene Expression
  • Genes, Recessive
  • Genetic Association Studies
  • Homozygote
  • Humans
  • Infant
  • Introns
  • Lebanon
  • Male
  • Mutation*
  • Pedigree
  • Poly-ADP-Ribose Binding Proteins / genetics*
  • Transcription Factors / genetics*

Substances

  • ERCC8 protein, human
  • Poly-ADP-Ribose Binding Proteins
  • Transcription Factors
  • DNA Helicases
  • ERCC6 protein, human
  • DNA Repair Enzymes