Intracerebral hemorrhage in a neonate with an intragenic COL4A2 duplication

Am J Med Genet A. 2021 Feb;185(2):571-574. doi: 10.1002/ajmg.a.61988. Epub 2020 Nov 28.

Abstract

Intracerebral hemorrhage is rare in term born neonates. Besides several non-genetic risk factors, pathogenic variants in COL4A1 and COL4A2 have been described to play a role in the pathophysiology of neonatal intracerebral hemorrhage. To the best of our knowledge, no intragenic COL4A2 duplications have been reported in humans to date. We report a neonate with intracerebral hemorrhage and a de novo intragenic COL4A2 duplication. Although it is not clear yet whether this genetic factor fully explains the clinical phenotype, it may have contributed at least as a risk factor for cerebral hemorrhage. Screening for intragenic COL4A1 and COL4A2 duplications as part of collagen IV diagnostics should be considered as part of the fetal and neonatal work-up for unexplained cerebral hemorrhages and to collect more evidence of the pathogenicity of this genetic mechanism.

Keywords: COL4A2; antenatal intracerebral hemorrhage; neonatal intracerbral haemorrhage.

Publication types

  • Case Reports

MeSH terms

  • Cerebral Hemorrhage / diagnosis
  • Cerebral Hemorrhage / diagnostic imaging
  • Cerebral Hemorrhage / genetics*
  • Cerebral Hemorrhage / pathology
  • Collagen Type IV / genetics*
  • Female
  • Fetus / diagnostic imaging
  • Fetus / pathology
  • Gene Duplication / genetics
  • Genetic Predisposition to Disease*
  • Humans
  • Infant, Newborn
  • Male
  • Mutation / genetics
  • Phenotype
  • Prenatal Diagnosis

Substances

  • COL4A1 protein, human
  • COL4A2 protein, human
  • Collagen Type IV