K Hallmann

Publications (7)9.25 Total impact

• Article: The voltage-gated sodium channel gene SCN2A and idiopathic generalized epilepsy.

  K Haug, K Hallmann, J Rebstock, J Dullinger, S Muth, F Haverkamp, H Pfeiffer, B Rau, C E Elger, P Propping, A Heils
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  ABSTRACT: We tested the hypothesis that genetic variation in the human sodium channel gene SCN2A confers liability to idiopathic generalized epilepsy (IGE). We performed a systematic search for mutations in 46 familial IGE cases and detected three novel polymorphisms, however, allele frequencies did not differ significantly between patients and controls. A rare mutation (R1918H) was identified in one patient but was absent in one further affected family member. Thus, our results do not suggest a major role of SCN2A in the etiology of IGE.
  Epilepsy Research 01/2002; 47(3):243-6. · 2.29 Impact Factor
• Article: The voltage-gated sodium channel beta2-subunit gene and idiopathic generalized epilepsy.

  K Haug, T Sander, K Hallmann, B Rau, J S Dullinger, C E Elger, P Propping, A Heils
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  ABSTRACT: Recent identification of ion channel gene mutations in Mendelian epilepsies suggests that genetically driven neuronal hyperexcitability plays an important role in epileptogenesis. In this study, we tested the hypothesis that genetic variation in the human SCN2B gene confers liability to common subtypes of idiopathic generalized epilepsies (IGE). A systematic search for mutations was performed in 92 IGE patients. We detected a novel single nucleotide polymorphism (SNP), however, allele frequencies did not differ between IGE patients and controls (chi2 = 0.19, df = 1, p = 0.744). Furthermore, a missense mutation in codon 209 (Asn209Pro) was identified in one patient, but was found to be absent in an affected sibling of the index patient. Thus, our results do not suggest a major role of the SCN2B gene in the etiology of common IGE subtypes.
  Neuroreport 09/2000; 11(12):2687-9. · 1.66 Impact Factor
• Article: Mutation screening of the chromosome 8q24.3-human activity-regulated cytoskeleton-associated gene (ARC) in idiopathic generalized epilepsy.

  K Haug, J Kremerskothen, K Hallmann, T Sander, J Dullinger, B Rau, S Beyenburg, M J Lentze, A Barnekow, C E Elger, P Propping, A Heils
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  ABSTRACT: Idiopathic generalized epilepsy (IGE) comprises a heterogeneous group of disorders, in which a high genetic predisposition and a complex mode of inheritance have been suggested. However, genes, which confer liability to common IGE subtypes including juvenile myoclonic epilepsy (JME) and childhood absence epilepsy (CAE) have not been identified so far. Here, we tested the hypothesis that genetic variation in the human homolog of the (ARC) contributes to the etiology of common IGE disorders. The gene has recently been mapped to chromosome 8q24.3, a region which spans previously identified major IGE susceptibility loci. A systematic search for mutations was performed in 143 patients with a known family history of IGE. However, no evidence for functional variants was found in the ARC coding sequence. Nevertheless, we detected a novel common C489T single nucleotide polymorphism, which provides a useful marker in genetic linkage and association studies. By performing a population- and family-based study we however failed to show significant association between this novel single nucleotide polymorphism and IGE, a finding, which most likely rules out that genetic variation in or close to the ARC gene confers liability to common IGE subtypes.
  Molecular and Cellular Probes 08/2000; 14(4):255-60. · 2.08 Impact Factor
• Article: Association analysis between a regulatory-promoter polymorphism of the human monoamine oxidase A gene and idiopathic generalized epilepsy.

  K Haug, T Sander, K Hallmann, M J Lentze, P Propping, C E Elger, A Heils
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  ABSTRACT: Monoaminergic neurotransmission plays an important role in the regulation of neuronal network excitability and seizure activity. Therapeutic inhibition of the mitochondrial enzyme monoamine oxidase A (MAO-A), which is involved in the degradation and inactivation of monoaminergic neurotransmitters, has been shown to confer a potent anticonvulsant effect. These and other findings suggest a possible role of the X-linked MAO-A gene in epileptogenesis. Therefore, our study was designed to test for an association between a novel MAO-A gene promoter polymorphism and common subtypes of idiopathic generalized epilepsy (IGE). The length of a 30-bp repetitive sequence approximately 1.2 kb upstream of the ATG initiation codon was assessed in 126 patients with juvenile myoclonic epilepsy (JME), 122 patients with idiopathic absence epilepsy (IAE), and 248 healthy controls of German descent. Both sexes were analyzed separately. Although we observed a trend towards a lower number of heterozygotes carrying the 3 and 4 copy alleles in female IAE patients (chi2 = 3.813, df = 1, P = 0.053), allele frequencies did not deviate significantly between patients and controls. Thus, our results do not provide evidence for a contribution of the functional MAO-A gene promoter polymorphism to the pathogenesis of common IGE subtypes.
  Epilepsy Research 05/2000; 39(2):127-32. · 2.29 Impact Factor
• Article: A KCNQ2 splice site mutation causing benign neonatal convulsions in a Scottish family.

  W L Lee, C Biervert, K Hallmann, A Tay, J C Dean, O K Steinlein
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  ABSTRACT: Benign familial neonatal convulsions (BFNC) are one of the rare idiopathic epilepsies with autosomal dominant mode of inheritance. Two voltage-gated potassium channels, KCNQ2 on chromosome 20q13.3 and KCNQ3 on 8q24, have been recently identified as the genes responsible for BFNC. Here we describe a large family with BFNC in which we found a previously undescribed mutation in the KCNQ2 gene. A 1187(+2)T/G nucleotide exchange affects the conserved donor splice site motif in intron 9. This mutation can be predicted to give rise to aberrant splicing of the primary transcript. There was a wide range of clinical manifestations in this family. An unusual clinical feature is the occurrence of partial seizures in later life with corresponding focal neurological deficits.
  Neuropediatrics 03/2000; 31(1):9-12. · 0.94 Impact Factor
• Article: Mutation analysis of the inwardly rectifying K(+) channels KCNJ6 (GIRK2) and KCNJ3 (GIRK1) in juvenile myoclonic epilepsy.

  K Hallmann, M Durner, T Sander, O K Steinlein
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  ABSTRACT: Genetic factors play a major role in the etiology of idiopathic generalized epilepsy. However, in most syndromes, especially the common ones, multiple genetic factors seem to be involved. Mutations in K(+) channel genes have previously found to be associated with epilepsy both in humans and in mice. The weaver mice phenotype, characterized by ataxia, tremor, male infertility, and tonic-clonic seizures, is caused by a point mutation in the inwardly rectifier K(+) channel gene KCNJ6 (GIRK2). A knockout mouse model deprived of functional KCNJ6 protein is susceptible to spontaneous and provoked seizures without showing the histological signs of neuronal cell death found in the weaver mouse. Thus, the KCNJ6 gene seems to play an important role in seizure control. We therefore performed a mutation analysis of KCNJ6 and the related KCNJ3 gene in 38 patients with juvenile myoclonic epilepsy (JME). Two novel same-sense nucleotide exchanges were identified, but none of these changed the coding sequence. These results do not support a major role for the KCNJ6/KCNJ3 heteromeric receptor in the etiology of JME. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:8-11, 2000
  American Journal of Medical Genetics 03/2000; 96(1):8-11.
• Article: Recurrent microdeletions at 15q11.2 and 16p13.11 predispose to idiopathic generalized epilepsies

  C.G.F. de Kovel, H. Trucks, I. Helbig, H.C. Mefford, C Baker, C. Leu, C. Kluck, H. Muhle, S. von Spiczak, P. Ostertag, [......], K M Klein, H M Hamer, F Rosenow, E.H. Brilstra, T.G.A. Kasteleijn-Nolst Trenité, M.E.M. Swinkels, B.P.C. Koeleman, D. Lindhout, E E Eichler, T Sander