Entire FGF12 duplication by complex chromosomal rearrangements associated with West syndrome.

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.

• Authors: Yoichiro Oda, Yuri Uchiyama, Ai Motomura, Atsushi Fujita, Yoshiteru Azuma, Yutaka Harita, Takeshi Mizuguchi, Kumiko Yanagi, Hiroko Ogata, Kenichiro Hata, Tadashi Kaname, Yoichi Matsubara, Keiko Wakui, Naomichi Matsumoto
• Journal: Journal of human genetics (J Hum Genet) Vol. 64 Issue 10 Pg. 1005-1014 (Oct 2019) ISSN: 1435-232X [Electronic] England
• PMID: 31311986 (Publication Type: Case Reports, Journal Article)

Chemical References

• FGF12 protein, human
• Fibroblast Growth Factors

Topics

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