Comprehensive Genomic Analysis of Patients With Disorders of Cerebral Cortical Development
PBN-AR
Instytucja
Instytut Matki i Dziecka
Informacje podstawowe
Główny język publikacji
angielski
Czasopismo
European Journal of Human Genetics (35pkt w roku publikacji)
ISSN
1018-4813
EISSN
Wydawca
NATURE PUBLISHING GROUP
DOI
URL
Rok publikacji
2018
Numer zeszytu
8
Strony od-do
1121-1131
Numer tomu
26
Identyfikator DOI
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Streszczenia
Język
angielski
Treść
Malformations of cortical development (MCDs) manifest with structural brain anomalies that lead to neurologic sequelae, including epilepsy, cerebral palsy, developmental delay, and intellectual disability. To investigate the underlying genetic architecture of patients with disorders of cerebral cortical development, a cohort of 54 patients demonstrating neuroradiologic signs of MCDs was investigated. Individual genomes were interrogated for single-nucleotide variants (SNV) and copy number variants (CNV) with whole-exome sequencing and chromosomal microarray studies. Variation affecting known MCDs-associated genes was found in 16/54 cases, including 11 patients with SNV, 2 patients with CNV, and 3 patients with both CNV and SNV, at distinct loci. Diagnostic pathogenic SNV and potentially damaging variants of unknown significance (VUS) were identified in two groups of seven individuals each. We demonstrated that de novo variants are important among patients with MCDs as they were identified in 10/16 individuals with a molecular diagnosis. Three patients showed changes in known MCDs genes and a clinical phenotype beyond the usual characteristics observed, i.e., phenotypic expansion, for a particular known disease gene clinical entity. We also discovered 2 likely candidate genes, CDH4, and ASTN1, with human and animal studies supporting their roles in brain development, and 5 potential candidate genes. Our findings emphasize genetic heterogeneity of MCDs disorders and postulate potential novel candidate genes involved in cerebral cortical development.
Cechy publikacji
oryginalny artykuł naukowy
research article
zrecenzowany naukowo
artykuł w czasopiśmie zagranicznym
Inne
System-identifier
PX-5de62e23d5de0f74df0c3a0b
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