PRRT2 mutations in familial infantile seizures, paroxysmal dyskinesia, and hemiplegic migraine.
OBJECTIVE
To perform a clinical and genetic study of a family with benign familial infantile seizures (BFIS) and, upon finding a PRRT2 gene mutation, to study a cohort of probands with a similar phenotype. We extended the study to all available family members to find out whether PRRT2 mutations cosegregated with additional symptoms.


METHODS
We carried out a clinical and genealogic study of a 3-generation family and of 32 additional probands with BFIS (11 families), infantile convulsions and paroxysmal choreoathetosis (ICCA) (9 families), BFIS/generalized epilepsy with febrile seizures plus (5 families), and sporadic benign neonatal or infantile seizures (7 probands/families). We performed a genetic study consisting of linkage analysis and PRRT2 screening of the 33 probands/families.


RESULTS
We obtained a positive linkage in the 16p11.3-q23.1 chromosomal region in the large BFIS family. Mutation analysis of PRRT2 gene revealed a c.649dupC (p.Arg217Profs*8) in all affected individuals. PRRT2 analysis of the 32 additional probands showed mutations in 10, 8 familial and 2 sporadic, probands. Overall we found PRRT2 mutations in 11 probands with a mutation rate of 11 out of 33 (33%). BFIS co-occurred with migraine and febrile seizures in 2 families, with childhood absence epilepsy in one family and with hemiplegic migraine in one family.


CONCLUSIONS
Our results confirm the predominant role of PRRT2 mutations in BFIS and expand the spectrum of PRRT2-associated phenotypes to include febrile seizures, childhood absence seizures, migraine, and hemiplegic migraine.
Pediatric Neurology and Neurogenetics Unit and Laboratories, A. Meyer Children's Hospital-University of Florence, Florence, Italy.
Carla
C
Marini
Valerio
V
Conti
Davide
D
Mei
Domenica
D
Battaglia
Donatella
D
Lettori
Emma
E
Losito
Grazia
G
Bruccini
Gaetano
G
Tortorella
Renzo
R
Guerrini
D004421:Dystonia / Q000175:diagnosis / Q000235:genetics*; D004832:Epilepsy, Absence / Q000175:diagnosis / Q000235:genetics; D020936:Epilepsy, Benign Neonatal; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D020325:Migraine with Aura / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D003294:Seizures, Febrile / Q000175:diagnosis / Q000235:genetics; D013036:Spasms, Infantile / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C569370:PRRT2 protein, human