The clinical significance of small copy number variants in neurodevelopmental disorders.

Background: Despite abundant evidence for pathogenicity of large copy number variants (CNVs) in neurodevelopmental disorders (NDDs), the individual significance of genome-wide rare CNVs <500 kb has not been well elucidated in a clinical context.

Methods: By high-resolution chromosomal microarray analysis, we investigated the clinical significance of all rare non-polymorphic exonic CNVs sizing 1-500 kb in a cohort of 714 patients with undiagnosed NDDs.

Results: We detected 96 rare CNVs <500 kb affecting coding regions, of which 58 (60.

[Genetic diagnostics of cancer diseases].

Cancer is caused by genetic alterations, but only 10% of the cancer diseases are inherited. The probability for an individual or a family of having inherited cancer, individual consequences of the respective results of genetic testing, as well as its costs and reimbursement by the health insurance must be addressed by expert genetic counseling which at-risk requires special expertise. Identification of a germline mutation which may predispose to a variety of different cancer types allows determination of an individual's specific life time risk in symptomatic as well as in a-symptomatic family members.

Lack of evidence of an allelic association of a functional GABRB3 exon 1a promoter polymorphism with idiopathic generalized epilepsy.

Purpose: Mutation screening and linkage disequilibrium mapping of the gene encoding the GABA(A) beta(3) subunit (GABRB3) identified a common genetic variant in the exon 1a promoter region (C-allele of rs4906902) which displayed a reduced transcriptional activity and showed a strong allelic association with childhood absence epilepsy (CAE). The present population-based association study tested whether the C-allele of rs4906902 confers susceptibility to CAE or other common syndromes of idiopathic generalized epilepsy (IGE) in a German sample.

Methods: Seven hundred and eighty unrelated German IGE patients (250 CAE, 123 juvenile absence epilepsy, 303 juvenile myoclonic epilepsy (JME), 104 epilepsy with generalized tonic-clonic seizures on awakening) and 559 healthy population controls were genotyped for the single nucleotide polymorphism (SNP) rs4906902.

A mutation in the GABA(A) receptor alpha(1)-subunit is associated with absence epilepsy.

Objective: To detect mutations in GABRA1 in idiopathic generalized epilepsy.

Methods: GABRA1 was sequenced in 98 unrelated idiopathic generalized epilepsy patients. Patch clamping and confocal imaging was performed in transfected mammalian cells.

Association analysis between the human interleukin 1beta (-511) gene polymorphism and susceptibility to febrile convulsions.

Recently, an association between a regulatory polymorphism in the gene encoding the pro-inflammatory cytokine interleukin (IL)-1beta and febrile convulsions (FC) has been reported. In this study we attempted to confirm these findings in a sample consisting of 99 FC patients and 126 ethnically matched controls. Since about 3% of all FC patients experience unprovoked seizures (epilepsy) later during life we furthermore genotyped 43 patients with non-lesional temporal lobe epilepsy who reported a history of FC.