Trio-based whole-exome sequencing of 168 patients with low-functioning ASD at Sun Yat-sen Memorial Hospital in Wu et al., 2025 identified a paternally-inherited loss-of-function variant in the PTCH1 gene in a patient clinically diagnosed with ASD based on DSM-5 criteria and presenting with global developmental delay/intellectual disability. A number of de novo variants in PTCH1, including a de novo loss-of-function variant and several de novo missense variants that are predicted to be deleterious, have been identified in ASD probands from the Simons Simplex Collection, the SPARK cohort, the MSSNG cohort, the Autism Sequencing Consortium, the iHART cohort, and a Japanese cohort of 262 ASD probands (Iossifov et al., 2014; Yuen et al., 2016; Takata et al., 2018; Ruzzo et al., 2019; Zhou et al., 2022; Fu et al., 2022). Autism spectrum disorder or autistic traits have been reported in a subset of individuals with PTCH1-associated disorders, including basal cell nevus syndrome and somatic overgrowth with macrocephaly (Delbroek et al., 2011; Klein et al., 2019; Mashayekhi et al., 2023). Alterations in hippocampal and cortical layer structure, activity, and social behavior were observed in female Ptch1 +/- mice (Jackson et al., 2020). A prevalence estimate of autism of 4% was made in a cohort of 109 individuals from Norway with basal cell naevus syndrome caused by pathogenic PTCH1 variants (Brandtzg et al., 2025).
Molecular Function
This gene encodes a member of the patched family of proteins and a component of the hedgehog signaling pathway. Hedgehog signaling is important in embryonic development and tumorigenesis. The encoded protein is the receptor for the secreted hedgehog ligands, which include sonic hedgehog, indian hedgehog and desert hedgehog. Following binding by one of the hedgehog ligands, the encoded protein is trafficked away from the primary cilium, relieving inhibition of the G-protein-coupled receptor smoothened, which results in activation of downstream signaling. Mutations of this gene have been associated with basal cell nevus syndrome and holoprosencephaly.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Predicting the diagnostic efficacy of trio-based whole exome sequencing in children with low-function autism spectrum disorders: a multicenter study
A novel de novo canonical splice site mutation in the PTCH1 gene in a male patient with mild psychomotor retardation and autistic traits: a case report
Heterozygous mutation of sonic hedgehog receptor (Ptch1) drives cerebellar overgrowth and sex-specifically alters hippocampal and cortical layer structure, activity, and social behavior in female mice
