title: High frequency of rare copy number variants affecting functionally related genes in patients with structural brain malformations.
abstract: During the past years, significant advances have been made in our understanding of the development of the human brain, and much of this knowledge comes from genetic studies of disorders associated with abnormal brain development. We employed array-comparative genomic hybridization (CGH) to investigate copy number variants (CNVs) in a cohort of 169 patients with various structural brain malformations including lissencephaly, polymicrogyria, focal cortical dysplasia, and corpus callosum agenesis. The majority of the patients had intellectual disabilities (ID) and suffered from symptomatic epilepsy. We detected at least one rare CNV in 38 patients (22.5%). All genes located within the rare CNVs were subjected to enrichment analysis for specific Gene Ontology Terms or Kyoto Encyclopedia of Genes and Genomes pathways and to protein-protein network analysis. Based on these analyses, we propose that genes involved in "axonal transport," "cation transmembrane transporter activity," and the "c-Jun N-terminal kinase (JNK) cascade" play a significant role in the etiology of brain malformations. This is to the best of our knowledge the first systematic study of CNVs in patients with structural brain malformations and our data show that CNVs play an important role in the etiology of these malformations, either as direct causes or as genetic risk factors.
authors: Kariminejad-Najmabadi Pathology and Genetics Center, Tehran, Iran.
authors: Roxana
authors: R
authors: Kariminejad
authors: Allan
authors: A
authors: Lind-Thomsen
authors: Zeynep
authors: Z
authors: Tümer
authors: Fikret
authors: F
authors: Erdogan
authors: Hans H
authors: HH
authors: Ropers
authors: Niels
authors: N
authors: Tommerup
authors: Reinhard
authors: R
authors: Ullmann
authors: Rikke S
authors: RS
authors: Møller
mesh_terms: D061085:Agenesis of Corpus Callosum / Q000000981:diagnostic imaging / Q000235:genetics; D001921:Brain / Q000000981:diagnostic imaging*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations / Q000235:genetics*; D004827:Epilepsy / Q000000981:diagnostic imaging / Q000235:genetics; D005260:Female; D018628:Gene Dosage / Q000235:genetics; D005787:Gene Frequency; D006801:Humans; D008607:Intellectual Disability / Q000000981:diagnostic imaging / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D009421:Nervous System Malformations / Q000000981:diagnostic imaging / Q000235:genetics*; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D011859:Radiography; D015898:Tomography Scanners, X-Ray Computed
chemical_list: D011506:Proteins