Clinical evaluation of 19 patients with a syndromic form of intellectual disability resulting from a recurrent de novo missense variant in the PACS1 gene (p.Arg203Trp) demonstrated that 6/19 individuals presented with ASD or showed behavior with the autism spectrum (Schuurs-Hoeijmakers et al., 2016). Functional characterization of the p.Arg203Trp variant showed that expression of mutant PACS1 mRNA in zebrafish embryos induced craniofacial defects (Schuurs-Hoeijmakers et al., 2012).
This gene encodes a protein with a putative role in the localization of trans-Golgi network (TGN) membrane proteins that contain acidic cluster sorting motifs. Controls the endosome-to-Golgi trafficking of furin and mannose-6-phosphate receptor by connecting the acidic-cluster-containing cytoplasmic domain of these molecules with the adapter-protein complex-1 (AP-1) of endosomal clathrin-coated membrane pits.
Type of Disorder
Clinical delineation of the PACS1-related syndrome-Report on 19 patients.
50pg human mutant PACS1 mRNA with with p.Arg203Trp substitution was injected into 2- to 4-cell-stage zebrafish embryos. Also, wild-type (control) or mutant RNA was injected in 2- to 4-cell-stage sox10::eGFP transgenic zebrafish embryos, which express green fluorescent protein (GFP) in cranial neural crest cells.
Allele Type: knockdown
Strain of Origin: Not specified
Genetic Background: Not specified
ES Cell Line: Not specified
Mutant ES Cell Line: Not specified
Model Source: 23159249