Cryptic chromosome deletions involving SCN1A in severe myoclonic epilepsy of infancy.
OBJECTIVE
To identify cryptic chromosomal deletions involving SCN1A in patients with severe myoclonic epilepsy of infancy (SMEI).


METHODS
Thirty-nine patients with SMEI and without SCN1A point mutations and their parents were typed with 14 intragenic SCN1A polymorphisms to identify hemizygosity. The parental origin and the extent of genomic deletions were determined by fluorescence in situ hybridization analysis using genomic clones encompassing chromosome 2q24.3-q31.1. Deletion breakpoints were more finely mapped by typing single-nucleotide polymorphisms and microsatellite markers.


RESULTS
We identified three patients with SMEI who had genomic deletions encompassing the SCN1A locus. Deletion size was between 607 kb and 4.7 Mb. Deletions originated de novo from paternal chromosome in all subjects. One patient had central precocious puberty and palatoschisis. Genotype-phenotype correlations suggest that these clinical features are due to genes centromeric to SCN1A.


CONCLUSIONS
Patients with severe myoclonic epilepsy of infancy (SMEI) lacking SCN1A point mutations should be investigated for cryptic chromosomal deletions involving SCN1A. Clinical features other than epilepsy could be associated with SMEI as a consequence of deletions in contiguous genes.
Madia
F
F
Muscle and Neurodegenerative Disease Unit, Institute G. Gaslini, University of Genova, Genova, Italy.
Striano
P
P
Gennaro
E
E
Malacarne
M
M
Paravidino
R
R
Biancheri
R
R
Budetta
M
M
Cilio
M R
MR
Gaggero
R
R
Pierluigi
M
M
Minetti
C
C
Zara
F
F
D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D004252:DNA Mutational Analysis; D004831:Epilepsies, Myoclonic / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D008297:Male; D009154:Mutation; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010290:Parents; D015222:Sodium Channels / Q000235:genetics*
D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels