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Review

PTCHD1: Identification and Neurodevelopmental Contributions of an Autism Spectrum Disorder and Intellectual Disability Susceptibility Gene

1
Molecular Neuropsychiatry and Development (MiND) Lab, Molecular Brain Science Research Department, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M5T 1RS, Canada
2
Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada
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Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada
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Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada
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Department of Psychology, University of Toronto, Toronto, ON M5S 3G3, Canada
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Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada
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Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada
*
Author to whom correspondence should be addressed.
Academic Editor: M. E. Suzanne Lewis
Genes 2022, 13(3), 527; https://doi.org/10.3390/genes13030527
Received: 1 February 2022 / Revised: 1 March 2022 / Accepted: 3 March 2022 / Published: 17 March 2022
(This article belongs to the Special Issue Genetic and Phenotypic Subtypes of Autism Spectrum Disorder)
Over the last one and a half decades, copy number variation and whole-genome sequencing studies have illuminated the considerable genetic heterogeneity that underlies the etiologies of autism spectrum disorder (ASD) and intellectual disability (ID). These investigations support the idea that ASD may result from complex interactions between susceptibility-related genetic variants (single nucleotide variants or copy number variants) and the environment. This review outlines the identification and neurobiological characterization of two such genes located in Xp22.11, Patched domain-containing 1 (PTCHD1), and its antisense lncRNA PTCHD1-AS. Animal models of Ptchd1 disruption have recapitulated a subset of clinical symptoms related to ASD as well as to ID. Furthermore, these Ptchd1 mouse knockout studies implicate the expression of Ptchd1 in both the thalamic and the hippocampal brain regions as being crucial for proper neurodevelopment and cognitive function. Altered kynurenine metabolic signalling has been postulated as a disease mechanism in one of these animal studies. Additionally, ASD patient-derived induced pluripotent stem cells (iPSCs) carrying a copy number loss impacting the antisense non-coding RNA PTCHD1-AS have been used to generate 2D neuronal cultures. While copy number loss of PTCHD1-AS does not affect the transcription of PTCHD1, the neurons exhibit diminished miniature excitatory postsynaptic current frequency, supporting its role in ASD etiology. A more thorough understanding of risk factor genes, such as PTCHD1 and PTCHD1-AS, will help to clarify the intricate genetic and biological mechanisms that underlie ASD and ID, providing a foundation for meaningful therapeutic interventions to enhance the quality of life of individuals who experience these conditions. View Full-Text
Keywords: PTCHD1; PTCHD1-AS; autism spectrum disorders; intellectual disability; neurodevelopment PTCHD1; PTCHD1-AS; autism spectrum disorders; intellectual disability; neurodevelopment
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MDPI and ACS Style

Pastore, S.F.; Ko, S.Y.; Frankland, P.W.; Hamel, P.A.; Vincent, J.B. PTCHD1: Identification and Neurodevelopmental Contributions of an Autism Spectrum Disorder and Intellectual Disability Susceptibility Gene. Genes 2022, 13, 527. https://doi.org/10.3390/genes13030527

AMA Style

Pastore SF, Ko SY, Frankland PW, Hamel PA, Vincent JB. PTCHD1: Identification and Neurodevelopmental Contributions of an Autism Spectrum Disorder and Intellectual Disability Susceptibility Gene. Genes. 2022; 13(3):527. https://doi.org/10.3390/genes13030527

Chicago/Turabian Style

Pastore, Stephen F., Sangyoon Y. Ko, Paul W. Frankland, Paul A. Hamel, and John B. Vincent. 2022. "PTCHD1: Identification and Neurodevelopmental Contributions of an Autism Spectrum Disorder and Intellectual Disability Susceptibility Gene" Genes 13, no. 3: 527. https://doi.org/10.3390/genes13030527

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