Elaborating the phenotypic spectrum associated with mutations in ARFGEF2: Case study and literature review

I Tanyalcin, H Verhelst, Dicky Halley, T Vanderhasselt, L Villard, C Goizet, W lissens, Grazia Verheijen - Mancini, AC (Anna) Jansen

Research output: Contribution to journalArticleAcademic

9 Citations (Scopus)


Background: The BIG2 protein, coded by ARFGEF2 indirectly assists neuronal proliferation and migration during cortical development. Mutations in ARFGEF2 have been reported as a rare cause of periventricular heterotopia. Methods: The presence of periventricular heterotopia, acquired microcephaly and suspected recessive inheritance led to mutation analysis of ARFGEF2 in two affected siblings and their healthy consanguineous parents, after mutations in FLNA had been ruled out. Results: A homozygous c.242_249delins7 (p.Pro81fs) mutation in exon 3 of ARFGEF2 was identified in the siblings. The alteration is a combination of 2 missense mutations (c.242C > A and c.247G > T) and a frameshift mutation (c.249delA) resulting in a premature stop codon. The clinical phenotype was characterized by dystonic quadriplegia, marked developmental delay, obstructive cardiomyopathy, recurrent infections and feeding difficulties. Degenerative features included early regression, acquired Conclusion: Mutations in ARFGEF2 can be anticipated based on characteristic clinical and imaging features. (C) 2013 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
Original languageUndefined/Unknown
Pages (from-to)666-670
Number of pages5
JournalEuropean Journal of Paediatric Neurology
Issue number6
Publication statusPublished - 2013

Research programs

  • EMC MGC-02-96-01

Cite this