Novel COL4A2 variant in a large pedigree: Consequences and dilemmas

Clin Genet. 2017 Oct;92(4):447-448. doi: 10.1111/cge.13016. Epub 2017 May 25.

Abstract

Pathogenic COL4A2 variants cause abnormalities in collagen production and can have serious implications for a range of organ systems, most notably the brain. Herein, we describe a large family of first-degree relatives affected by a novel heterozygous variant in COL4A2 (c.3490G.A). A wide disease spectrum is described, from asymptomatic to symptomatic, including 2 children with porencephaly and co-existing juvenile idiopathic polyarthritis. During a subsequent pregnancy, antenatal testing identified a positive fetus. In view of the literature, we review management and genetic counselling dilemmas.

Keywords: COL4A2; arthritis; cerebral palsy; genetics; neurology.

Publication types

  • Letter

MeSH terms

  • Arthritis, Juvenile / complications
  • Arthritis, Juvenile / genetics*
  • Arthritis, Juvenile / physiopathology
  • Bone Diseases, Developmental
  • Brain / metabolism
  • Brain / physiopathology
  • Collagen / biosynthesis
  • Collagen / genetics
  • Collagen / metabolism*
  • Collagen Type IV / genetics*
  • Craniofacial Abnormalities
  • Female
  • Heterozygote
  • Humans
  • Hyperostosis
  • Hypertelorism
  • Male
  • Mutation
  • Pedigree
  • Phenotype
  • Porencephaly / complications
  • Porencephaly / genetics*
  • Porencephaly / physiopathology

Substances

  • COL4A2 protein, human
  • Collagen Type IV
  • Collagen

Supplementary concepts

  • Schwartz-Lelek syndrome