Somatic and germline mosaicisms in severe myoclonic epilepsy of infancy.
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.
Gennaro
Elena
E
Laboratory of Muscle Pathology and Neurogenetics, Unit of Muscular and Neurodegenerative Disease, Istituto G. Gaslini, University of Genova, Italy.
Santorelli
Filippo M
FM
Bertini
Enrico
E
Buti
Daniela
D
Gaggero
Roberto
R
Gobbi
Giuseppe
G
Lini
Marcella
M
Granata
Tiziana
T
Freri
Elena
E
Parmeggiani
Antonia
A
Striano
Pasquale
P
Veggiotti
Pierangelo
P
Cardinali
Simona
S
Bricarelli
Franca Dagna
FD
Minetti
Carlo
C
Zara
Federico
F
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*
D007477:Ions; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels