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Record W1923721795 · doi:10.1111/cge.12482

Phenotypic spectrum associated with <i><scp>PTCHD1</scp></i> deletions and truncating mutations includes intellectual disability and autism spectrum disorder

2014· article· en· W1923721795 on OpenAlexafffund
Ayeshah Chaudhry, Abdul Noor, Bryan Degagne, Kate Baker, Levinus A. Bok, Angela F. Brady, David Chitayat, Brian Hon‐Yin Chung, Cheryl Cytrynbaum, David A. Dyment, Isabel Filges, Benjamin M. Helm, H. Terry Hutchison, LJB Jeng, Frédéric Laumonnier, Christian R. Marshall, M. Menzel, Sandhya Parkash, Michael Parker, Lucy F. Raymond, Andrea L. Rideout, Wendy Roberts, Rosemarie Rupps, Ina Schanze, C. T. R. M. Schrander‐Stumpel, Marsha Speevak, Dimitri J. Stavropoulos, Servi J.C. Stevens, Elizabeth R. Thomas, Annick Toutain, Samantha A. Schrier Vergano, Rosanna Weksberg, Stephen W. Scherer, John B. Vincent, M. T. Carter

Bibliographic record

VenueClinical Genetics · 2014
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenomic variations and chromosomal abnormalities
Canadian institutionsOntario Institute for Cancer ResearchCredit Valley HospitalTrillium Health CentreChildren's & Women's Health Centre of British ColumbiaIzaak Walton Killam Health CentreChildren's Hospital of Eastern OntarioDalhousie UniversityOntario Medical AssociationSickKids FoundationUniversity of TorontoMount Sinai HospitalCentre for Addiction and Mental HealthUniversity of British ColumbiaHospital for Sick Children
FundersFondation de FranceEuropean CommissionCanadian Institutes of Health ResearchGenome CanadaNational Institute for Health and Care ResearchWellcomeOntario Genomics InstituteAcademy of Medical SciencesWellcome Trust
KeywordsIntellectual disabilityAutism spectrum disorderHypotoniaAutismNeurodevelopmental disorderGeneticsPhenotypePsychologyCopy-number variationGlobal developmental delayDevelopmental disorderNeuropsychologyPervasive developmental disorderCognitionNeuroscienceBiologyPsychiatryGene

Abstract

fetched live from OpenAlex

Studies of genomic copy number variants (CNVs) have identified genes associated with autism spectrum disorder (ASD) and intellectual disability (ID) such as NRXN1, SHANK2, SHANK3 and PTCHD1. Deletions have been reported in PTCHD1 however there has been little information available regarding the clinical presentation of these individuals. Herein we present 23 individuals with PTCHD1 deletions or truncating mutations with detailed phenotypic descriptions. The results suggest that individuals with disruption of the PTCHD1 coding region may have subtle dysmorphic features including a long face, prominent forehead, puffy eyelids and a thin upper lip. They do not have a consistent pattern of associated congenital anomalies or growth abnormalities. They have mild to moderate global developmental delay, variable degrees of ID, and many have prominent behavioral issues. Over 40% of subjects have ASD or ASD-like behaviors. The only consistent neurological findings in our cohort are orofacial hypotonia and mild motor incoordination. Our findings suggest that hemizygous PTCHD1 loss of function causes an X-linked neurodevelopmental disorder with a strong propensity to autistic behaviors. Detailed neuropsychological studies are required to better define the cognitive and behavioral phenotype.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.005
Threshold uncertainty score0.016

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0050.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.014
GPT teacher head0.257
Teacher spread0.244 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations72
Published2014
Admission routes2
Has abstractyes

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