Protocadherin 19 mutations in girls with infantile-onset epilepsy
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Abstract
Objective: To explore the causative role of PCDH19 gene (Xq22) in female patients with epilepsy.
Methods: We studied a cohort of 117 female patients with febrile seizures (FS) and a wide spectrum of epilepsy phenotypes including focal and generalized forms with either sporadic or familial distribution.
Results: PCDH19 screening showed point mutations in 13 probands (11%). Mean age at seizure onset was 8.5 months; 8 patients (62%) presented with FS, 4 (33%) with cluster of focal seizures, and 1 with de novo status epilepticus (SE). Subsequent seizure types included afebrile tonic-clonic, febrile, and afebrile SE, absences, myoclonic, and focal seizures. Seven patients (54%) had a clinical diagnosis consistent with Dravet syndrome (DS); 6 (46%) had focal epilepsy. In most patients, seizures were particularly frequent at onset, manifesting in clusters and becoming less frequent with age. Mental retardation was present in 11 patients, ranging from mild (7; 64%) to moderate (1; 9%) to severe (3; 27%). Five patients (38%) had autistic features in association to mental retardation. Mutations were missense (6), truncating (2), frameshift (3), and splicing (2). Eleven were new mutations. Mutations were inherited in 3 probands (25%): 2 from apparently unaffected fathers and 1 from a mother who had had generalized epilepsy.
Conclusions: PCDH19 is emerging as a major gene for infantile-onset familial or sporadic epilepsy in female patients with or without mental retardation. In our cohort, epileptic encephalopathy with DS-like features and focal epilepsy of variable severity were the associated phenotypes and were equally represented.
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Supplemental data at www.neurology.org
Study funding: Supported by the Sixth Framework Thematic Priority Life Sciences, Genomics and Biotechnology for Health (LSH-CT-2006-037315-EPICURE) and by the Mariani Foundation Research Grant, Milan, Italy.
Disclosure: Author disclosures are provided at the end of the article.
Received January 25, 2010. Accepted in final form May 7, 2010.
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Letters: Rapid online correspondence
- Protocadherin 19 mutations in girls with infantile-onset epilepsy
- Rima Nabbout, Department of Pediatric Neurology and Metabolic Diseases, Hospital Necker Enfants Malades, 149 rue de Sevres, 75015 Paris, Francerimanabbout@yahoo.com
- Christel Depienne (Paris, France; christel.depienne@upmc.fr), Catherine Chiron (Paris, France; catherine.chiron@nck.aphp.fr), Olivier Dulac (Paris, France; olivier.dulac@nck.aphp.fr)
Submitted December 02, 2010 - Reply from the authors
- Carla Marini, Child Neurology Unit, Pediatric Hospital A. Meyer, viale Pieraccini 24, 50133 Florence, Italyc.marini@meyer.it
- Renzo Guerrini (Florence, Italy, r.guerrini@meyer.it)
Submitted December 02, 2010
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