Parental SCN1A mutation mosaicism in familial Dravet syndrome

@article{Selmer2009ParentalSM,
  title={Parental SCN1A mutation mosaicism in familial Dravet syndrome},
  author={Kaja K. Selmer and A S Eriksson and Kristin Brandal and Thore Egeland and Chantal M. E. Tallaksen and D. E. Undlien},
  journal={Clinical Genetics},
  year={2009},
  volume={76}
}
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… 
Mechanisms for variable expressivity of inherited SCN1A mutations causing Dravet syndrome
TLDR
It is indicated that mosaicism is found in at least 7% of families with DS, and additional genetic or environmental factors likely modulate the severity of the expression of the mutation.
Mosaic SCN1A mutations in familial partial epilepsy with antecedent febrile seizures
TLDR
This is the first report of mosaic SCN1A mutations in families with probands that do not exhibit DS, but manifest only a milder phenotype, and such families with mild cases should be approached with caution in genetic counseling and the possibility of mosaicism origin associated with high recurrence risk should be excluded.
Mosaicism of a missense SCN1A mutation and Dravet syndrome in a Roma/Gypsy family
TLDR
A Roma/Gypsy family is described, where a missense mutation in SCN1A, p.D194N, is transmitted from a mosaic GEFS+ father to a child with Dravet syndrome.
Parental mosaicism in another case of Dravet syndrome caused by a novel SCN1A deletion: a case report
TLDR
These cases confirm parental mosaicism in the transmission of Dravet syndrome and add to the spectrum of known mutations of the SCN1A gene.
Molecular genetics of Dravet syndrome
  • P. de Jonghe
  • Medicine
    Developmental medicine and child neurology
  • 2011
TLDR
These patients initially may have all characteristics of Dravet syndrome but may later run a somewhat different course, and the yield of SCN1A mutations detected varied from 50 to 80%, implying that other genes or factors must be involved in these ‘SCN 1A‐negative Dravets’.
Molecular genetics of Dravet syndrome: Review
TLDR
These patients initially may have all characteristics of Dravet syndrome but may later run a somewhat different course, and the yield of SCN1A mutations detected varied from 50 to 80%, implying that other genes or factors must be involved in these ‘SCN 1A-negative Dravets’.
Dravet syndrome: a genetic epileptic disorder.
TLDR
Dravet syndrome, or severe myoclonic epilepsy in infancy, is one of the most severe types of genetic epilepsy, and is considered as a model of channelopathy.
Recurrence risk of epilepsy and mental retardation in females due to parental mosaicism of PCDH19 mutations
TLDR
It is shown that gonadal mosaicism of a PCDH19 mutation in a parent is an important molecular mechanism associated with the inheritance of EFMR and should be considered when providing genetic counseling for couples who have one affected daughter as they may risk recurrence of affected daughters and having sons at risk of transmitting EFMR.
Assessment of parental mosaicism in SCN1A-related epilepsy by single-molecule molecular inversion probes and next-generation sequencing
TLDR
Single-molecule molecular inversion probes (smMIP), a technique with high sensitivity for detecting low-grade mosaic variants and high cost-effectiveness, are used to investigate the incidence of parental mosaicism of SCN1A variants in a cohort of 90 families and assess the feasibility of this technique.
Mosaicism of de novo pathogenic SCN1A variants in epilepsy is a frequent phenomenon that correlates with variable phenotypes
TLDR
This data indicates that mosaicism, caused by postzygotic mutation, is a major modifier in SCN1A‐related epilepsy, and the importance of identifying modifying factors in this patient group is stressed.
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