Deletion of the SCN gene cluster on 2q24.4 is associated with severe epilepsy: an array-based genotype-phenotype correlation and a comprehensive review of previously published cases.
Epilepsy Res
; 81(1): 69-79, 2008 Sep.
Article
em En
| MEDLINE
| ID: mdl-18539002
ABSTRACT
PURPOSE:
To characterize a deletion of chromosome 2q at the molecular level in a patient suffering from severe epilepsy resembling severe myoclonic epilepsy of infancy/Dravet's syndrome (SMEI/DS) and to correlate other cases harboring deletions in the same region to morphological and clinical data.METHODS:
Array-based comparative genomic hybridization (array CGH) was performed on DNA from the patient. Forty-three previously published cases reporting deletions within region 2q21-q31 were collected and analyzed regarding their cytogenetic and clinical data.RESULTS:
A del(2)(q24.3q31.1) was detected in the patient, spanning a 10.4-megabase (Mb) region between 165.18 and 175.58Mb, harboring 47 genes. FISH analysis was performed, confirming this deletion. Twenty-two of the 43 previously published cases were seizure-positive. The most common dysmorphic features were ear abnormalities, microcephaly, micrognathia and brachysyndactyly for all patients as well as for solely the seizure-positive and -negative ones. For the 22 seizure-positive cases chromosome subband 2q24.3 constituted the smallest commonly deleted region among the majority of the cases, where subbands 2q22.1 and 2q33.3 represented the most proximal and distal breakpoint, respectively.CONCLUSIONS:
Based on the early age of presentation and the severity of the epilepsy reported for the majority of the seizure-positive cases it was concluded that SMEI/DS could be the epileptic encephalopathy associated with deletions within the 2q22.1-q33.3 region, due to haploinsuffiency of SCN1A and/or complete or partial deletion of other voltage-gated sodium channel genes caused by the aberration. Furthermore, our study supports that array CGH is a competent technique for screening SCN1A mutation-negative patients diagnosed with SMEI/DS-like epilepsies and dysmorphic features, generating rapid and high-resolution data of genomic imbalances present in the patients.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Canais de Sódio
/
Deleção de Genes
/
Epilepsia Mioclônica Juvenil
Tipo de estudo:
Risk_factors_studies
Limite:
Female
/
Humans
/
Newborn
Idioma:
En
Revista:
Epilepsy Res
Assunto da revista:
CEREBRO
/
NEUROLOGIA
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Suécia
País de publicação:
HOLANDA
/
HOLLAND
/
NETHERLANDS
/
NL
/
PAISES BAJOS
/
THE NETHERLANDS