Entire FGF12 duplication by complex chromosomal rearrangements associated with West syndrome

J Hum Genet. 2019 Oct;64(10):1005-1014. doi: 10.1038/s10038-019-0641-1. Epub 2019 Jul 16.

Abstract

Complex rearrangements of chromosomes 3 and 9 were found in a patient presenting with severe epilepsy, developmental delay, dysmorphic facial features, and skeletal abnormalities. Molecular cytogenetic analysis revealed 46,XX.ish der(9)(3qter→3q28::9p21.1→9p22.3::9p22.3→9qter)(RP11-368G14+,RP11-299O8-,RP11-905L2++,RP11-775E6++). Her dysmorphic features are consistent with 3q29 microduplication syndrome and inv dup del(9p). Trio-based WES of the patient revealed no pathogenic single nucleotide variants causing epilepsy, but confirmed a 3q28q29 duplication involving FGF12, which encodes fibroblast growth factor 12. FGF12 positively regulates the activity of voltage-gated sodium channels. Recently, only one recurrent gain-of-function variant [NM_021032.4:c.341G>A:p.(Arg114His)] in FGF12 was found in a total of 10 patients with severe early-onset epilepsy. We propose that the patient's entire FGF12 duplication may be analogous to the gain-of-function variant in FGF12 in the epileptic phenotype of this patient.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Chromosome Deletion
  • Chromosome Disorders / genetics*
  • Chromosome Disorders / physiopathology
  • Chromosome Duplication / genetics*
  • Chromosomes, Human, Pair 3 / genetics
  • Chromosomes, Human, Pair 9
  • DNA Copy Number Variations
  • Exome Sequencing
  • Female
  • Fibroblast Growth Factors / genetics*
  • Gene Duplication
  • Humans
  • Infant
  • Neurodevelopmental Disorders / etiology
  • Neurodevelopmental Disorders / genetics*
  • Neurodevelopmental Disorders / physiopathology
  • Pedigree
  • Spasms, Infantile / genetics*
  • Spasms, Infantile / physiopathology
  • Translocation, Genetic

Substances

  • FGF12 protein, human
  • Fibroblast Growth Factors

Supplementary concepts

  • Chromosome 3q29 Duplication Syndrome
  • Chromosome 9 inversion or duplication
  • Chromosome 9, partial monosomy 9p