A de novo complex chromosomal rearrangement with breakpoints disrupting the intronic sequence of the RAB19, PPFIA1, and SHANK2 genes was identified in a 3.5-year-old male patient with moderate ID, speech delay, autistic behavior, and facial dysmorphism (Schluth-Bolard et al., 2013). A rare de novo missense variant that was predicted to be probably damaging was identified in the PPFIA1 gene in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014; yeast two-hybrid experiments in Chen et al., 2018 demonstrated that this variant disrupted the interaction of PPFIA1 with several genes, including the ASD candidate gene PPP2R5D.
The protein encoded by this gene is a member of the LAR protein-tyrosine phosphatase-interacting protein (liprin) family. Liprins interact with members of LAR family of transmembrane protein tyrosine phosphatases, which are known to be important for axon guidance and mammary gland development. This protein binds to the intracellular membrane-distal phosphatase domain of tyrosine phosphatase LAR, and appears to localize LAR to cell focal adhesions. This interaction may regulate the disassembly of focal adhesion and thus help orchestrate cell-matrix interactions.
Type of Disorder
Breakpoint mapping by next generation sequencing reveals causative gene disruption in patients carrying apparently balanced chromosome rearrangemen...