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. CONCLUSION: 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.
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. CONCLUSION: 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.
Authors: Sarah E Heron; Bronwyn E Grinton; Sara Kivity; Zaid Afawi; Sameer M Zuberi; James N Hughes; Clair Pridmore; Bree L Hodgson; Xenia Iona; Lynette G Sadleir; James Pelekanos; Eric Herlenius; Hadassa Goldberg-Stern; Haim Bassan; Eric Haan; Amos D Korczyn; Alison E Gardner; Mark A Corbett; Jozef Gécz; Paul Q Thomas; John C Mulley; Samuel F Berkovic; Ingrid E Scheffer; Leanne M Dibbens Journal: Am J Hum Genet Date: 2012-01-13 Impact factor: 11.025
Authors: X Wang; W Sun; X Zhu; L Li; T Du; W Mao; X Wu; H Wei; S Zhu; Y Sun; Y Liu; N Niu; Y Wang; Y Liu Journal: Eur J Neurol Date: 2010-02-10 Impact factor: 6.089
Authors: P M C Callenbach; E H van den Boogerd; R F M de Coo; R ten Houten; J C Oosterwijk; G Hageman; R R Frants; O F Brouwer; A M J M van den Maagdenberg Journal: Clin Genet Date: 2005-06 Impact factor: 4.438
Authors: R Caraballo; S Pavek; A Lemainque; M Gastaldi; B Echenne; J Motte; P Genton; R Cersósimo; V Humbertclaude; N Fejerman; A P Monaco; M G Lathrop; J Rochette; P Szepetowski Journal: Am J Hum Genet Date: 2001-02-13 Impact factor: 11.025
Authors: N Schwarz; A Hahn; T Bast; S Müller; H Löffler; S Maljevic; E Gaily; I Prehl; S Biskup; T Joensuu; A-E Lehesjoki; B A Neubauer; H Lerche; U B S Hedrich Journal: J Neurol Date: 2015-12-08 Impact factor: 4.849