Mutation in filamin A causes periventricular heterotopia, developmental regression, and West syndrome in males

Mutation in filamin A causes periventricular heterotopia, developmental regression, and West syndrome in males

Author Masruha, Marcelo Rodrigues Autor UNIFESP Google Scholar
Caboclo, Luis Otávio Sales Ferreira Autor UNIFESP Google Scholar
Carrete Junior, Henrique Autor UNIFESP Google Scholar
Cendes, Iscia L. Google Scholar
Rodrigues, Murilo Gimenes Autor UNIFESP Google Scholar
Garzon, Eliana Autor UNIFESP Google Scholar
Yacubian, Elza Márcia Targas Autor UNIFESP Google Scholar
Sakamoto, Américo Ceiki Autor UNIFESP Google Scholar
Sheen, Volney Google Scholar
Harney, Megan Google Scholar
Neal, Jason Google Scholar
Sean Hill, R. Google Scholar
Bodell, Adria Google Scholar
Walsh, Christopher Google Scholar
Vilanova, Luiz Celso Pereira Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade Estadual de Campinas (UNICAMP)
Fed Univ Espirito Santo
Harvard Univ
Abstract Purpose: Familial periventricular heterotopia (PH) represents a disorder of neuronal migration resulting in multiple gray-matter nodules along the lateral ventricular walls. Prior studies have shown that mutations in the filamin A (FLNA) gene can cause PH through an X-linked dominant pattern. Heterozygotic female patients usually remain asymptomatic until the second or third decade of life, when they may have predominantly focal seizures, whereas hemizygotic male fetuses typically die in utero. Recent studies have also reported mutations in FLNA in male patients with PH who are cognitively normal. We describe PH in three male siblings with PH due to FLNA, severe developmental regression, and West syndrome.Methods: the study includes the three affected brothers and their parents. Video-EEG recordings and magnetic resonance image (MRI) scanning were performed on all individuals. Mutations for FLNA were detected by using polymerase chain reaction (PCR) on genomic DNA followed by single-stranded conformational polymorphism (SSCP) analysis or sequencing.Results: Two of the siblings are monozygotic twins, and all had West syndrome with hypsarrthymia on EEG. MRI of the brain revealed periventricular nodules of cerebral gray-matter intensity, typical for PH. Mutational analyses demonstrated a cytosine-to-thymidine missense mutation (c. C1286T), resulting in a threonine-to-methionine amino acid substitution in exon 9 of the FLNA gene.Conclusions: the association between PH and West syndrome, to our knowledge, has not been previously reported. Males with PH have been known to harbor FLNA mutations, although uniformly, they either show early lethality or survive and have a normal intellect. the current studies show that FLNA mutations can cause periventricular heterotopia, developmental regression, and West syndrome in male patients, suggesting that this type of FLNA mutation may contribute to severe neurologic deficits.
Keywords subependymal heterotopia
periventricular heterotopia
West syndrome
Language English
Date 2006-01-01
Published in Epilepsia. Oxford: Blackwell Publishing, v. 47, n. 1, p. 211-214, 2006.
ISSN 0013-9580 (Sherpa/Romeo, impact factor)
Publisher Blackwell Publishing
Extent 211-214
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000234403200028

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