title: Somatic and germline mosaicisms in severe myoclonic epilepsy of infancy.
abstract: Severe Myoclonic Epilepsy in Infancy (SMEI) is an intractable epileptic syndrome with onset in the first year of life and is commonly caused by de novo mutations in the SCN1A gene, encoding the alpha1-subunit of the neuronal voltage-gated sodium channel. We report two unrelated families in which probands were affected by SMEI and their parents showed a single febrile seizure during early childhood or no neurological symptoms. Semiquantitative analysis of SCN1A mutations allowed the detection of a somatic and germline mosaicism in one of the parents. The study provides the first example of parental mosaicisms in SMEI and opens a new insight into the phenotypic variability and complex inheritance of this condition. The identification of germline mosaicisms has important consequences in genetic counseling of SMEI when SCN1A mutations appear to occur de novo with standard screening methods.
authors.affiliation: Laboratory of Muscle Pathology and Neurogenetics, Unit of Muscular and Neurodegenerative Disease, Istituto G. Gaslini, University of Genova, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Gennaro
authors.forename: Filippo M
authors.initials: FM
authors.lastname: Santorelli
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
authors.forename: Daniela
authors.initials: D
authors.lastname: Buti
authors.forename: Roberto
authors.initials: R
authors.lastname: Gaggero
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gobbi
authors.forename: Marcella
authors.initials: M
authors.lastname: Lini
authors.forename: Tiziana
authors.initials: T
authors.lastname: Granata
authors.forename: Elena
authors.initials: E
authors.lastname: Freri
authors.forename: Antonia
authors.initials: A
authors.lastname: Parmeggiani
authors.forename: Pasquale
authors.initials: P
authors.lastname: Striano
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Veggiotti
authors.forename: Simona
authors.initials: S
authors.lastname: Cardinali
authors.forename: Franca Dagna
authors.initials: FD
authors.lastname: Bricarelli
authors.forename: Carlo
authors.initials: C
authors.lastname: Minetti
authors.forename: Federico
authors.initials: F
authors.lastname: Zara
mesh_terms: D000483:Alleles; D002851:Chromatography, High Pressure Liquid; D002874:Chromosome Mapping; D004831:Epilepsies, Myoclonic / Q000235:genetics*; D005192:Family Health; D005260:Female; D016368:Frameshift Mutation; D008040:Genetic Linkage; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D007477:Ions / Q000378:metabolism; D008297:Male; D018895:Microsatellite Repeats; D009030:Mosaicism; D009154:Mutation; D020125:Mutation, Missense; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000378:metabolism; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D035781:Siblings; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D007477:Ions; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels