Diagnostic yield of chromosomal microarray and trio whole exome sequencing in congenital brain anomalies

Introduction The deductive method: from karyotyping to aCGH and WES is an important aspect in the diagnosis search for causes of intellectual disability due congenital brain anomalies. There recommendation exclude presence CNV or monogenic variants patients with a normal karyotype, but clinical picture syndromic disease. Objectives Improvement disability. Methods 60K Agilent microarrays, SureSelect Human All Exon V8 Results Pathogenic potentially pathogenic CNVs were excluded previously by 10 families (total 32 people, 2 had children) anomalies (for example, polymicrogyria, pachygyria, lissencephaly). identified candidate all that can lead impaired neurodevelopment, including 3 families, likely three other uncertain significance 4 families. Almost these de novo , except one family, where proband has been compound heterozygous two RELN gene. first case mutation was detected girl agenesis corpus callosum. It missense DYNC1H1 (NM_001376.5): c.4868G>A (p.Arg1623Gln), which leads development autosomal dominant type 13 (OMIM 614563). second variant boy callosum agenesis, pontine hypogenesis, pachygyria frontal lobes. MACF1 (ENST00000567887.5): c.21989A>G(p.Asp7330Gly), lissencephaly 9 complex brainstem malformation third found epilepsy myelination white matter parietal-occipital areas cerebral hemispheres. CDKL5 (NM_001323289.2):c.404-1G>A developmental epileptic encephalopathy 300672). Conclusions Sixteen responsible mental health reported this study. Most changes genes. arisen novo. Trio-based shown be step making genetic if chromosomal subchromosomal abnormalities excluded. description patient most correct interpretation results, allows establish exact cause disease several unclear identified. This study supported Russian Science Foundation, grant 21-65-00017, https://rscf.ru/project/21-65-00017/ Disclosure Interest None Declared