Putative Relation Between Autism Spectrum Disease & Hereditary Multiple Exostosis Investigated by Whole Genome Sequencing & Comparative Genome Analyses in a Family with ASD and HME with EXT-1 Mutations

A family with two male children affected with ASD and HME as well as an unaffected female child, was studied to identify the Genetic basis of ASD in the family and the possible relation between ASD & HME. Irie et al., [PNAS, 109: 5052–5056, 2012] reported that Heparan Sulfate deficient mice due to inactivating EXT-1 mutations exhibit Autism-like socio-communicative deficits and stereotypies suggesting a relation between MHE and ASD. The father and both male children are clinically affected by HME and carry the known pathogenic EXT-1 c.C1018T/p.R340C dominant mutation. Both male children are also affected by ASD; the father is not. The mother and the female child are not affected either by HME or ASD and do not carry the EXT-1 mutation. Whole-Genome SNP genotyping and CNV analyses did not detect aneuploidy or deletion/duplication defects as possible ASD causes. WGNGS for all members, comparative genome analyses and data mining were as follows: [Only exonic variants considered, prioritized according to incr...