Elaborating the phenotypic spectrum associated with mutations in ARFGEF2: Case study and literature review
European Journal of Paediatric Neurology. 2013-11-01; 17(6): 666-670
DOI: 10.1016/J.EJPN.2013.05.002
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1. Eur J Paediatr Neurol. 2013 Nov;17(6):666-70. doi: 10.1016/j.ejpn.2013.05.002.
Epub 2013 Jun 4.
Elaborating the phenotypic spectrum associated with mutations in ARFGEF2: case
study and literature review.
Tanyalçin I(1), Verhelst H, Halley DJ, Vanderhasselt T, Villard L, Goizet C,
Lissens W, Mancini GM, Jansen AC.
Author information:
(1)Centre for Medical Genetics, UZ Brussel, Brussels, Belgium.
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 microcephaly and cerebral atrophy. Brain MRI revealed
bilateral periventricular heterotopia, small corpus callosum, cerebral and
hippocampal atrophy and hyperintensity in the putamen.
CONCLUSION: Mutations in ARFGEF2 can be anticipated based on characteristic
clinical and imaging features.
Copyright © 2013 European Paediatric Neurology Society. Published by Elsevier
Ltd. All rights reserved.
DOI: 10.1016/j.ejpn.2013.05.002
PMID: 23755938 [Indexed for MEDLINE]