Our objective was to identify and characterize pathogenic variants in individuals with autistic spectrum disorders (ASD) with developmental delay and seizures. These features are a group of diseases caused by at least 700 different genes. A number of cases remain genetically undiagnosed.
We performed exome (protein coding sequences from all genes) sequencing to identify pathogenic variants in two unrelated undiagnosed individuals. Our study identifies SCAMP5 gene deficiency as a cause for their disease and underscores the importance of trafficking in neuronal synapses. We performed functional studies in the Drosophila melanogaster model to assess the protein function in vivo. (By Dr. Claude Besmond, https://jmg.bmj.com/content/early/2019/08/23/jmedgenet-2018-105927 )
(A) and (B) show the pedigree and Sanger chromatograms for families 1 and 2 respectively. (C) is a graphical representation of the SCAMP5 protein showing the cytoplasmic location of the p.Gly180Trp variant. (D) shows the exons and domains structure of SCAMP5 and the aligments across differents species of the protein sequences.