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ABSTRACT: The aim of this study was to replicate a previously reported association between drug resistance in epilepsy patients and the 24C>T variant of the ABCC2 gene that codes for the drug efflux transporter MRP2.
We genotyped 381 Caucasian epileptic patients (337 drug resistant and 44 drug responsive) and 247 healthy controls for the ABCC2 gene -24C>T polymorphism (rs717620) and two other nearby SNPs in linkage disequilibrium (1249G>A and 3972C>T). Genotype, allele and three-SNP-haplotype frequencies were compared between groups. Patients were further stratified into four groups according to their degree of drug resistance (as measured by seizure frequency under medication) to perform regression analysis against genotypes and haplotpyes.
We detected no significant differences in the distribution of any of the tested alleles, genotypes or haplotypes between the investigated groups. Neither was there an association between genotypes or haplotypes and degree of drug resistance. This study was adequately powered to detect genotype relative risks of above two.
Although adequately powered to detect the previously reported effect size and although our definition of drug resistance, following the International League Against Epilepsy guidelines, was slightly stricter than in the original study, we failed to confirm an association between the 24C>T variant in the ABCC2 gene and drug resistance in epilepsy.
Pharmacogenomics 01/2012; 13(2):185-90. · 3.97 Impact Factor
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ABSTRACT: Mutations in the valosin-containing protein (VCP) are known to cause autosomal-dominant inclusion-body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD). We report a novel missense mutation (G157R) in the N-terminal region of the VCP gene in a German family. Family members presented with mild to moderate proximal muscle weakness, Paget disease of bone, and signs of early cognitive decline, with onset in the fourth decade. Two family members also showed signs of early hearing impairment, which was confirmed to be sensorineural in one person, a symptom not yet described in the context of IBMPFD.
Muscle & Nerve 03/2009; 39(3):389-91. · 2.37 Impact Factor
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ABSTRACT: Mutations in the gene SLITRK1 (Slit and Trk-like 1) have been reported in patients with Tourette's disorder (TD). We sequenced the entire SLITRK1 gene including the coding region the 5' and 3' untranslated region in 92 Austrian patients with TD. No nucleotide changes within the protein-coding region were identified. One patient was found to carry a variant within the 3' untranslated region (3383g>a), which was absent in 192 control individuals and which segregated in two additional family members with tic symptoms. In conclusion, our results provide no evidence for SLITRK1 playing a major role in TD.
Psychiatric genetics 12/2008; 18(6):308-9. · 2.33 Impact Factor
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Epilepsia 07/2008; 49(6):1108-9. · 3.96 Impact Factor
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ABSTRACT: We systematically analyzed the lateralizing value of clinical seizure semiology in patients with frontal lobe epilepsy (FLE).
We studied the incidence, positive predictive value (PPV), and the lateralizing significance of various clinical symptoms in 228 seizures (s) of 31 patients (p) with medically refractory FLE (17 with left-sided and 14 with right-sided seizure onset). Seizures recorded during prolonged video-EEG monitoring were assessed by two independent reviewers blinded for the patient's clinical data. Analysis was performed both for patients and seizures.
Version [16 p (52%); PPV, 94%; p=0.001; 47 s (21%); PPV, 75%; p=0.001], unilateral clonic movements [16 p (52%); PPV, 81%; p=0.021; 32 s (14%); PPV, 81%; p=0.001], unilateral dystonic posturing [eight p (26%); PPV, 75%; p=0.289; 46 s (20%); PPV, 80%; p=0.001], unilateral tonic posturing [10 p (32%); PPV, 80%; p=0.109; 19 s (7.4%); PPV, 79%; p=0.019], and unilateral grimacing [10 p (32%); PPV, 100%; p=0.002; 19 s (8%); PPV, 100%; p=0.001] were of lateralizing significance, indicating a contralateral seizure onset. Asymmetric ending [five p (16%); PPV, 80%; p=0.375; nine s (4%); PPV, 89%; p=0.039] after secondarily generalized tonic-clonic seizures was significantly associated with an ipsilateral seizure onset. Pure ictal vocalizations occurred significantly more frequently in seizures of right hemispheric onset [13 p (42%); PPV, 62%; p=0.581; 63 s (28%); PPV, 73%; p=0. 001], whereas in individual patients, this symptom showed no lateralizing significance. The remaining clinical symptoms (figure 4 sign, unilateral hand automatisms, early head turning, postictal nose wiping, and unilateral eye blinking) were not of lateralizing significance in our patients. The results of clinical seizure lateralization corresponded with the final lateralization of the seizure-onset zone in 81% of our patients.
Clinical seizure semiology can provide correct information on the lateralization of the seizure-onset zone in >80% of patients with medically refractory frontal lobe epilepsy.
Epilepsia 03/2007; 48(3):517-23. · 3.96 Impact Factor
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ABSTRACT: Recently a coding nonsynonymous single-nucleotide polymorphism (SNP; G1465A) in the GABBR1 gene was reported to be associated with the incidence and severity of temporal lobe epilepsy (TLE). To clarify the role of this polymorphism in TLE, we attempted to replicate this study.
We genotyped 188 unrelated patients with TLE (110 women, 78 men) and 259 controls of middle European descent by a restriction-length polymerase chain reaction (PCR) assay.
Only two (0.5%) patients and none of the controls exhibited the heterozygous A/G genotype, which was previously reported to be overrepresented among patients as compared with controls.
Although our study was sufficiently powered, we could not replicate the original association. Potential reasons for this failure could lie in subtle genetic differences between the studied populations or differences in the TLE phenotypes.
Epilepsia 03/2006; 47(2):437-9. · 3.96 Impact Factor
