Pathogenic sequence variant in the GNAI1 gene were recently introduced as a cause of novel syndrome with a manifestation of variable developmental delay and autistic features. In our study, we report a case of monozygotic twins with severe intellectual disability and motor delay and developmental dysphasia. Both probands and their parents were examined using multi-step molecular diagnostic algorithm including whole-exome sequencing (WES), resulting in the identification of a novel, de novo pathogenic sequence variant in the GNAI1 gene, NM_002069.6:c.815 A>G, p.(Asp272Gly) in probands. Using WES we also verified the microarray findings of a familial 8q24.23q24.3 duplication and heterozygous 5q13.2 deletion, not associated with clinical symptoms in probands. Our results confirmed the role of the GNAI1 gene in the pathogenesis of syndromic neurodevelopmental disorders. They support trio- or quatro-based WES as a suitable molecular diagnostics method for the simultaneous detection of clinically relevant sequence variants and CNVs in individuals with neurodevelopmental disorders and rare diseases.

Biosciences Institute Newcastle University Newcastle upon Tyne UK

Department of Biology and Medical Genetics 2nd Faculty of Medicine Charles University Prague and Faculty Hospital Motol Prague Czech Republic

Department of Experimental Biology Faculty of Science Masaryk University Brno Czech Republic

Department of Medical Genetics and Genomics University Hospital Brno Brno Czech Republic

Laboratory of Cytogenomics Centre of Molecular Biology and Genetics Department of Internal Medicine Haematology and Oncology University Hospital Brno Brno Czech Republic

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