title: Parental SCN1A mutation mosaicism in familial Dravet syndrome.
abstract: Different SCN1A mutations are known to cause a variety of phenotypes, such as generalized epilepsy with febrile seizures plus (GEFS+), Dravet syndrome and familial hemiplegic migraine (FHM). In Dravet syndrome, most mutations are de novo and familial cases are rare. In this study, Dravet syndrome is observed in two maternal half sisters. They have healthy fathers and their common mother has never experienced seizures, but has a lifelong history of migraine. Direct sequencing of DNA extracted from blood revealed a heterozygous SCN1A nonsense mutation c.3985C>T in the sisters, but not in the mother. The mutation induces a premature stop codon and probably leads to a non-functional protein. Further examination of the mother's DNA showed that she has a mosaicism of the mutation. This report of parental SCN1A nonsense mutation mosaicism in familial Dravet syndrome suggests that mosaicism might be more common than previously suspected and emphasizes the importance of taking mosaicism into account in genetic counselling of Dravet syndrome and SCN1A mutations. Furthermore, whether the migraine of the mother could be influenced by her SCN1A mutation mosaicism is not known, but increased awareness of migraine in future studies of SCN1A related epilepsies could clarify this intriguing link between migraine and epilepsy.
authors: Department of Medical Genetics, Oslo University Hospital, Ullevaal Hospital, Oslo, Norway. k.k.selmer@medisin.uio.no
authors: K K
authors: KK
authors: Selmer
authors: A-S
authors: AS
authors: Eriksson
authors: K
authors: K
authors: Brandal
authors: T
authors: T
authors: Egeland
authors: C
authors: C
authors: Tallaksen
authors: D E
authors: DE
authors: Undlien
mesh_terms: D001483:Base Sequence; D018389:Codon, Nonsense / Q000235:genetics*; D004831:Epilepsies, Myoclonic / Q000235:genetics*; D005260:Female; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D008969:Molecular Sequence Data; D009030:Mosaicism; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D017422:Sequence Analysis, DNA; D035781:Siblings; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels