NR APNA
AU Walz,R.; Castro,R.M.R.P.S.; Velasco,T.R.; Alexandre,V.Jr.; Lopes,M.H.; Leite,J.P.; Santos,A.C.; Assirati,J.A.Jr.; Wichert-Ana,L.; Terra-Bustamante,V.C.; Bianchin,M.M.; Maciag,P.C.; Ribeiro,K.B.; Guarnieri,R.; Araujo,D.; Caballero,O.L.; Moura,R.; Salim,A.C.; Kindlmann,K.; Landemberger,M.C.; Marques,W.Jr.; Fernandes,R.M.; Serafini,L.N.; Machado,H.R.; Carlotti,C.G.Jr.; Brentani,R.R.; Sakamoto,A.C.; Martins,V.R.
TI Surgical outcome in mesial temporal sclerosis correlates with prion protein gene variant
QU Neurology 2003 Nov 11; 61(9): 1204-10
KI Neurology. 2003 Nov 11;61(9):1168-9. PMID: 14610113
PT clinical trial; controlled clinical trial; journal article
AB BACKGROUND: Mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) is the most common surgically remediable epileptic syndrome. Ablation of the cellular prion protein (PrPc) gene (PRNP) enhances neuronal excitability of the hippocampus in vitro and sensitivity to seizure in vivo, indicating that PrPc might be related to epilepsy. OBJECTIVE: To evaluate the genetic contribution of PRNP to MTLE-HS. METHODS: The PRNP coding sequence of DNA from peripheral blood cells of 100 consecutive patients with surgically treated MTLE-HS was compared to that from a group of healthy controls adjusted for sex, age, and ethnicity (n = 180). The presence of PRNP variant alleles was correlated with clinical and presurgical parameters as well as surgical outcome. RESULTS: A variant allele at position 171 (Asn -> Ser), absent in controls, was found in heterozygosis (Asn171Ser) in 23% of patients (p < 0.0001). The PRNP genotypes were not correlated with any clinical or presurgical data investigated. However, patients carrying the Asn171Ser variant had a five times higher chance of continuing to have seizures after temporal lobectomy (95% CI 1.65 to 17.33, p = 0.005) than those carrying the normal allele. At 18 months after surgery, 91.8% of patients with the normal allele at codon 171 were seizure free, in comparison to 68.2% of those carrying Asn171Ser (p = 0.005). CONCLUSIONS: The PRNP variant allele Asn171Ser is highly prevalent in patients with medically untreatable MTLE-HS and influences their surgical outcome. The results suggest that the PRNP variant allele at codon 171 (Asn171Ser) is associated with epileptogenesis in MTLE-HS.
MH Adult; Amino Acid Substitution; Brain Chemistry; DNA/analysis; Disease-Free Survival; Epilepsy, Temporal Lobe/complications/*physiopathology/*surgery; Ethnic Groups/statistics & numerical data; Female; Gene Frequency; Hippocampus/pathology; Human; Magnetic Resonance Imaging; Male; Odds Ratio; Prions/*genetics; Sclerosis/complications/*genetics/pathology; Sex Distribution; Support, Non-U.S. Gov't; Treatment Outcome; Variation (Genetics)/*genetics
AD CIREP, Centro de Cirurgia de Epilepsia, Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo (FMRP-USP), Ribeirao Preto, Brazil. rogerwalz@hotmail.com
SP englisch
PO USA