Exonic Deletions in AUTS2 Cause a Syndromic Form of Intellectual Disability and Suggest a Critical Role for the C Terminus

摘要: Genomic rearrangements involving AUTS2 (7q11.22) are associated with autism and intellectual disability (ID), although evidence for causality is limited. By combining the results of diagnostic testing 49,684 individuals, we identified 24 microdeletions that affect at least one exon AUTS2, as well translocation inversion each a breakpoint within locus. Comparison 17 well-characterized individuals enabled identification variable syndromic phenotype including ID, autism, short stature, microcephaly, cerebral palsy, facial dysmorphisms. The dysmorphic features were more pronounced in persons 3′ deletions. This part gene shown to encode C-terminal isoform (with an alternative transcription start site) expressed human brain. Consistent our genetic data, suppression auts2 zebrafish embryos caused microcephaly could be rescued by either full-length or AUTS2. Our observations demonstrate causal role neurocognitive disorders, establish hitherto unappreciated this locus, show how transcriptional complexity can underpin pathology. model provides valuable tool investigating etiology syndrome facilitating gene-function analysis future.