Mutations and deletions in PCDH19 account for various familial or isolated epilepsies in females.
Mutations in PCDH19, encoding protocadherin 19 on chromosome X, cause familial epilepsy and mental retardation limited to females or Dravet-like syndrome. Heterozygous females are affected while hemizygous males are spared, this unusual mode of inheritance being probably due to a mechanism called cellular interference. To extend the mutational and clinical spectra associated with PCDH19, we screened 150 unrelated patients (113 females) with febrile and afebrile seizures for mutations or rearrangements in the gene. Fifteen novel point mutations were identified in 15 female patients (6 sporadic and 9 familial cases). In addition, qPCR revealed two whole gene deletions and one partial deletion in 3 sporadic female patients. Clinical features were highly variable but included almost constantly a high sensitivity to fever and clusters of brief seizures. Interestingly, cognitive functions were normal in several family members of 2 families: the familial condition in family 1 was suggestive of Generalized Epilepsy with Febrile Seizures Plus (GEFS+) whereas all three affected females had partial cryptogenic epilepsy. These results show that mutations in PCDH19 are a relatively frequent cause of epilepsy in females and should be considered even in absence of family history and/or mental retardation.
Département de génétique et cytogénétique, Hôpital de la Pitié-Salpêtrière, Paris, France. christel.depienne@upmc.fr
Christel
C
Depienne
Oriane
O
Trouillard
Delphine
D
Bouteiller
Isabelle
I
Gourfinkel-An
Karine
K
Poirier
François
F
Rivier
Patrick
P
Berquin
Rima
R
Nabbout
Denys
D
Chaigne
Dominique
D
Steschenko
Agnès
A
Gautier
Dorota
D
Hoffman-Zacharska
Annie
A
Lannuzel
Marilyn
M
Lackmy-Port-Lis
Hélène
H
Maurey
Anne
A
Dusser
Marie
M
Bru
Brigitte
B
Gilbert-Dussardier
Agathe
A
Roubertie
Anna
A
Kaminska
Sandra
S
Whalen
Cyril
C
Mignot
Stéphanie
S
Baulac
Gaetan
G
Lesca
Alexis
A
Arzimanoglou
Eric
E
LeGuern
D000293:Adolescent; D000328:Adult; D015820:Cadherins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D011110:Polymorphism, Genetic; D000091363:Protocadherins; D055815:Young Adult
D015820:Cadherins; C438605:PCDH19 protein, human; D000091363:Protocadherins