Centrotemporal spikes in families with rolandic epilepsy

Neubauer, Bernd A.; Fiedler, Barbara; Himmelein, B.; Kampfer, F.; Lässker, Uta; Schwabe, Georg C.; Spanier, I.; Tams, D.; Bretscher, C.; Moldenhauer, K. A. K.; Kurlemann, G; Weise, Sebastian; Tedroff, Kristina; Eeg‐Olofsson, Orvar; Wadelius, Claes; Stephani, Ulrich

doi:10.1212/wnl.51.6.1608

Cited by 207 publications

(118 citation statements)

References 18 publications

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“…Another approach was taken to test the acetylcholine receptor subunits as candidate genes in a group of small families with benign epilepsy of childhood with centrotemporal spikes (51). A partial genome scan was carried out using markers in the chromosome regions containing the receptor subunit genes.…”

Section: Association Studies Using Candidate Genesmentioning

confidence: 99%

Identification of Epilepsy Genes in Human and Mouse

et al. 2001

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The development of molecular markers and genomic resources has facilitated the isolation of genes responsible for rare monogenic epilepsies in human and mouse. Many of the identified genes encode ion channels or other components of neuronal signaling. The electrophysiological properties of mutant alleles indicate that neuronal hyperexcitability is one cellular mechanism underlying seizures. Genetic heterogeneity and allelic variability are hallmarks of human epilepsy. For example, mutations in three different sodium channel genes can produce the same syndrome, GEFS+, while individuals with the same allele can experience different types of seizures. Haploinsufficiency for the sodium channel SCN1A has been demonstrated by the severe infantile epilepsy and cognitive deficits in heterozygotes for de novo null mutations. Large-scale patient screening is in progress to determine whether less severe alleles of the genes responsible for monogenic epilepsy may contribute to the common types of epilepsy in the human population. The development of pharmaceuticals directed towards specific epilepsy genotypes can be anticipated, and the introduction of patient mutations into the mouse genome will provide models for testing these targeted therapies.

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Section: Association Studies Using Candidate Genesmentioning

confidence: 99%

Identification of Epilepsy Genes in Human and Mouse

et al. 2001

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“…9 Alterations in a7nAChR are reported to cause seizures and neuropsychiatric disturbances in the affected individuals with an incomplete dominant inheritance pattern. [4][5][6]8,[10][11][12] One large genomic database survey identified 19 individuals with isolated heterozygous CHRNA7 gene deletions and 1 with an isolated homozygous deletion. 13 The neurological symptoms in individuals with isolated CHRNA7 deletions implicate CHRNA7 as the major candidate gene responsible for the predominant manifestations of 15q13.3 microdeletion syndrome.…”

Section: Introductionmentioning

confidence: 99%

Genome-wide gene expression in a patient with 15q13.3 homozygous microdeletion syndrome

Pichon

Kibiryeva

et al. 2013

Eur J Hum Genet

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We identified a novel homozygous 15q13.3 microdeletion in a young boy, with a complex neurodevelopmental disorder characterized by severe cerebral visual impairment with additional signs of congenital stationary night blindness, congenital hypotonia with areflexia, profound intellectual disability, and refractory epilepsy. The mechanisms by which the genes in the deleted region exert their effect are unclear. In this paper, we probed the role of downstream effects of the deletions as a contributing mechanism to the molecular basis of the observed phenotype. We analyzed gene expression of lymphoblastoid cells derived from peripheral blood of the proband and his relatives to ascertain the relative effects of the homozygous and heterozygous deletions. We identified 267 genes with apparent differential expression between the proband with the homozygous deletion and 3 age-and sex-matched typically developing controls. Several of the differentially expressed genes are known to influence neurodevelopment and muscular function, and thus may contribute to the observed cognitive impairment and hypotonia. We further investigated the role of CHRNA7 by measuring TNFa modulation (a potentially important pathway in regulating synaptic plasticity). We found that the cell line with the homozygous deletion lost the ability to inhibit the activation of tumor necrosis factor-a secretion. Our findings suggest downstream genes that may have been altered by the 15q13.3 homozygous deletion, and thus contributed to the severe developmental encephalopathy of the proband. Furthermore, we show that a potentially important pathway in learning and development is affected by the deletion of CHRNA7.

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“…The P50 sensory gating deficit, one of the best supported endophenotypes of schizophrenia and bipolar disorder, is strongly linked to this region, 1 as are two idiopathic epilepsies. 2,3 Of the many attempts to demonstrate linkage of schizophrenia and bipolar disorder to this region, two studies showed linkage to bipolar disorder, 4,5 but several found either weak [6][7][8][9][10] or no linkage to schizophrenia. [11][12][13] Both schizophrenia and bipolar disorder have also shown association with 15q13.3 markers.…”

Section: Introductionmentioning

confidence: 99%

Association between the 2-bp deletion polymorphism in the duplicated version of the alpha7 nicotinic receptor gene and P50 sensory gating

et al. 2012

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There is considerable evidence implicating the 15q13.3 region in neuropsychiatric disorders, with the a7 nicotinic receptor gene CHRNA7 the most plausible candidate. This region has multiple duplications and many copy number variants (CNVs). A common CNV involves a partial duplication of CHRNA7 (CHRFAM7A), which occurs in either orientation. We examined the distribution of these alternative genomic arrangements in a large cohort of psychiatric patients, their relatives and controls using the 2-bp deletion polymorphism as a marker for the orientation of CHRFAM7A. We investigated three common alleles for association with psychosis and with the P50 sensory gating deficit, which is strongly associated with psychosis and strongly linked to 15q13.3. We found significant within-family association with P50 (empirical P ¼ 0.004), which is robust to population stratification. Most of the effect came from the 2-bp deletion allele, which tags the variant of CHRFAM7A in the same orientation as CHRNA7. This allele is associated with the presence of the P50 sensory gating deficit (empirical P ¼ 0.0006). Tests comparing within-family and between-family components of association suggest considerable population stratification in the sample. We found no evidence for association with psychosis, but this may reflect lower power using this phenotype. Four out of six previous association studies found association of different psychiatric phenotypes with the same 2-bp deletion allele.

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Centrotemporal spikes in families with rolandic epilepsy

Cited by 207 publications

References 18 publications

Identification of Epilepsy Genes in Human and Mouse

Identification of Epilepsy Genes in Human and Mouse

Genome-wide gene expression in a patient with 15q13.3 homozygous microdeletion syndrome

Association between the 2-bp deletion polymorphism in the duplicated version of the alpha7 nicotinic receptor gene and P50 sensory gating

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