We previously reported a 167 Kb microdeletion of exon 1 of PTCHD1 (NM_ 173495.2) on chromosome Xp22.11 (3). PTCHD1 has three exons spanning ~62 Kb and it is predicted to encode a protein of 888 amino acids. In silico analysis suggests that PTCHD1 is a transmembrane protein containing a patched-related domain with twelve transmembrane helices, highly related to the Hedgehog (Hh) receptors PATCHED1 (PTCH1) and PTCH2 as well as to Niemann-Pick Type C1 protein (NPC1). Hh is one of the key signaling pathways involved in the formation of the neural tube and brain, specifically the differentiation of motor neurons ventrally and commissural interneurons dorsally (11,12). Mutations in Sonic Hedgehog, SHH (MIM 600725), have been reported in patients with developmental abnormalities, delay in speech acquisition and learning disabilities (13). Niemann-Pick disease type C1 also involves neurological and intellectual deficits (MIM 257220). This led us to investigate a possible role for PTCHD1 as a candidate gene for ASD and ID.
