title: The expanding phenotypic spectrum of ARFGEF2 gene mutation: Cardiomyopathy and movement disorder.
abstract: Mutations in ADP-ribosylation factor guanine nucleotide-exchange factor 2 (ARFGEF2) gene was recently recognized to cause bilateral periventricular nodular heterotopia, putaminal hyperintensity and movement disorder. A ten year-old girl with severe developmental and growth delay, feeding problems and involuntary movements is presented. Bilateral periventricular nodular heterotopia and putaminal hyperintensity were detected in cranial magnetic resonance imaging. Her echocardiographic examination revealed left ventricular non-compaction cardiomyopathy. Sequence analysis of ARFGEF2 gene demonstrated a homozygous c.5126G>A, p.Trp1709(∗) mutation. The mutation is the first nonsense mutation described in ARFGEF2 gene and the case is the second reported case of ARFGEF2 gene mutation with cardiomyopathy. The presented case supports the view that the presence of cardiomyopathy in ARFGEF2 gene mutations is more than a coincidence and thus expands the phenotypic spectrum of ARFGEF2 gene mutations. Mutations in the ARFGEF2 gene must be considered in the presence of bilateral periventricular nodular heterotopia and putaminal hyperintensity in children presenting with movement disorder, severe developmental delay and microcephaly. In case of ARFGEF2 gene mutation, screening for cardiomyopathy may be indicated.
authors.affiliation: Ege University Medical Faculty, Department of Pediatrics, Division of Child Neurology, Izmir, Turkey. Electronic address: sanem.yilmaz@ege.edu.tr.
authors.forename: Sanem
authors.initials: S
authors.lastname: Yilmaz
authors.affiliation: Ege University Medical Faculty, Department of Pediatrics, Division of Child Neurology, Izmir, Turkey.
authors.forename: Sarenur
authors.initials: S
authors.lastname: Gokben
authors.affiliation: Ege University Medical Faculty, Department of Pediatrics, Division of Child Neurology, Izmir, Turkey.
authors.forename: Gul
authors.initials: G
authors.lastname: Serdaroglu
authors.affiliation: Ege University Medical Faculty, Department of Radiology, Division of Neuroradiology, Izmir, Turkey.
authors.forename: Cenk
authors.initials: C
authors.lastname: Eraslan
authors.affiliation: Erasmus Medical Center, Department of Clinical Genetics, Rotterdam, The Netherlands.
authors.forename: Grazia M S
authors.initials: GM
authors.lastname: Mancini
authors.affiliation: Ege University Medical Faculty, Department of Pediatrics, Division of Child Neurology, Izmir, Turkey.
authors.forename: Hande
authors.initials: H
authors.lastname: Tekin
authors.affiliation: Ege University Medical Faculty, Department of Pediatrics, Division of Child Neurology, Izmir, Turkey.
authors.forename: Hasan
authors.initials: H
authors.lastname: Tekgul
mesh_terms: D001921:Brain / Q000473:pathology*; D009202:Cardiomyopathies / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002648:Child; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D009069:Movement Disorders / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D010641:Phenotype
chemical_list: C119088:ARFGEF2 protein, human; D018389:Codon, Nonsense; D020662:Guanine Nucleotide Exchange Factors
keywords: Cardiomyopathy; Movement disorder; Periventricular heterotopia; Putaminal hyperintensity