Biochemical and Biophysical Research Communications
Somatic and germline mosaicisms in Severe Myoclonic Epilepsy of Infancy
Section snippets
Material and methods
Selection of families and mutational analysis. We selected two families segregating a frameshift and a splice-site SCN1A mutation in two SMEI siblings (Fig. 1) from the screening of 138 patients. Detailed inclusion criteria and screening methods were previously reported [11]. Family 1 has been previously described [5]. We collected different tissue samples from all family members including peripheral lymphocytes, buccal epithelium, hair follicles, and urinary cells. Furthermore, we obtained a
Clinical presentation of the selected families
Detailed clinical histories of the affected subjects from the two families are described in appendix. Briefly, proband of family 1 (subject III:5) and her sib (III:6) started before the age of 10 months suffering from afebrile and febrile, generalized and focal seizures, and myoclonic jerks. Psychomotor delay and ataxia appeared after the onset of epilepsy. Electroencephalograms (EEGs) variably showed focal and generalized epileptic abnormalities. Antiepileptic therapy did not allow seizure
Discussion
In order to determine whether mosaicism could explain the reduced penetrance and variable expressivity of SCN1A mutations in the two SMEI families, we evaluated the amount of mutant cells in different tissues and found a somatic mosaicism in one and a germline mosaicism in another.
In family 1, the mother of two SMEI siblings carries a frameshift mutation in about 70–80% of cells and is not affected by epilepsy. Genotype–phenotype correlations in SCN1A-related disorders have been proved to be
Acknowledgments
We thank the families for their kind cooperation. This work has been supported by the Italian Ministry of Health (F.Z.) and the Pierfranco and Luisa Mariani Foundation ONLUS (F.Z.).
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