Mosaicism of a missense SCN1A mutation and Dravet syndrome in a Roma/Gypsy family.
SCN1A mutations account for a large proportion of Dravet syndrome patients, and are reported in other cases of epilepsy, such as some families with genetic epilepsy with febrile seizures plus (GEFS+). While most Dravet syndrome cases are caused by de novo mutations, 5% inherit a mutation from a mildly affected or symptom-free parent. Parental mosaicism has been identified, with documented cases involving truncating mutations or gene rearrangements. We describe a Roma/Gypsy family, where a missense mutation in SCN1A, p.D194N, is transmitted from a mosaic GEFS+ father to a child with Dravet syndrome. Mosaicism may be more common than assumed and should be considered regardless of the nature of the mutation.
Azmanov
Dimitar N
DN
Laboratory for Molecular Genetics, Centre for Medical Research and Western Australian Institute for Medical Research, The University of Western Australia, Perth, Australia. dazmanov@waimr.uwa.edu.au
Zhelyazkova
Sashka
S
Dimova
Petya S
PS
Radionova
Melania
M
Bojinova
Veneta
V
Florez
Laura
L
Smith
Shelagh J
SJ
Tournev
Ivailo
I
Jablensky
Assen
A
Mulley
John
J
Scheffer
Ingrid
I
Kalaydjieva
Luba
L
Sander
Josemir W
JW
D000293:Adolescent; D000483:Alleles; D004569:Electroencephalography; D004827:Epilepsy / Q000235:genetics*; D005500:Follow-Up Studies; D006580:Genetic Carrier Screening; D006801:Humans; D008297:Male; D009030:Mosaicism; D020125:Mutation, Missense / Q000235:genetics*; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D006178:Romani People / Q000235:genetics*; D003294:Seizures, Febrile / Q000175:diagnosis / Q000235:genetics*; D012815:Signal Processing, Computer-Assisted; D015222:Sodium Channels / Q000235:genetics*; D013577:Syndrome
D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels