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From the Neurogenetics Laboratory (F.M., P.S., R.B., C.M., F.Z.), Muscle and Neurodegenerative Disease Unit, Institute "G. Gaslini," University of Genova, Genetics Laboratory (F.M., E.G., M.M., R.P., M.P.), E.O. Ospedali Galliera, Genova, Pediatrics Unit (M.B.), Ospedale "S. Maria Incoronata Dell'Olmo," Cava de' Tirreni, Division of Neurology (M.R.C.), "Bambino Gesù" Children's Hospital, Rome, and Epilepsy Center (R.G.), Unit of Child Neurology and Psychiatry, Institute "G. Gaslini Institute," Genova, Italy.
Address correspondence and reprint requests to Dr. F. Zara, Neurogenetics Laboratory, Muscle and Neurodegenerative Disease Unit, Istituto Giannina Gaslini, University of Genova, Largo G. Gaslini 5, 16147 Genova, Italy; e-mail: federicozara{at}ospedale-gaslini.ge.it
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.
Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the October 10 issue to find the title link for this article.
*These authors contributed equally to this work
Supported by the Italian League Against Epilepsy and the Italian Ministry of Health (no. 132/03 to F.Z and C.M.). DNA samples and cell lines of patients and families are stored at the Galliera Genetic Bank (supported by Telethon Italy, grant no. C42).
Disclosure: The authors report no conflicts of interest.
Received March 15, 2006. Accepted in final form June 12, 2006.
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