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Record W3095196237 · doi:10.1111/cge.13877

PIGH deficiency can be associated with severe neurodevelopmental and skeletal manifestations

2020· article· en· W3095196237 on OpenAlexafffund
Camille Tremblay‐Laganière, Rauan Kaiyrzhanov, Reza Maroofian, Thi Tuyet Mai Nguyen, Kamran Salayev, Ilana Chilton, Wendy K. Chung, Jill A. Madden, Chanika Phornphutkul, Pankaj B. Agrawal, Henry Houlden, Philippe M. Campeau

Bibliographic record

VenueClinical Genetics · 2020
Typearticle
Languageen
FieldMedicine
TopicLysosomal Storage Disorders Research
Canadian institutionsCentre Hospitalier Universitaire Sainte-Justine
FundersNational Institute of Child Health and Human DevelopmentUCLH Biomedical Research CentreMedical Research CouncilNational Institutes of HealthFonds de Recherche du Québec - SantéEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentBoston Children's HospitalRosetrees TrustSimons Foundation Autism Research InitiativeWellcome TrustCanadian Institutes of Health ResearchJPB FoundationIntellectual and Developmental Disabilities Research Center
KeywordsMicrocephalyHypotoniaAutism spectrum disorderPhenotypeSpeech delayDysarthriaIntellectual disabilityHearing lossGlobal developmental delayMedicineLanguage delayApraxiaPsychomotor retardationAutismNeurodevelopmental disorderGeneticsPediatricsBiologyPathologyPsychologyAudiologyGeneLanguage developmentPsychiatry

Abstract

fetched live from OpenAlex

Phosphatidylinositol Glycan Anchor Biosynthesis class H (PIGH) is an essential player in the glycosylphosphatidylinositol (GPI) synthesis, an anchor for numerous cell membrane-bound proteins. PIGH deficiency is a newly described and rare disorder associated with developmental delay, seizures and behavioral difficulties. Herein, we report three new unrelated families with two different bi-allelic PIGH variants, including one new variant p.(Arg163Trp) which seems associated with a more severe phenotype. The common clinical features in all affected individuals are developmental delay/intellectual disability and hypotonia. Variable clinical features include seizures, autism spectrum disorder, apraxia, severe language delay, dysarthria, feeding difficulties, facial dysmorphisms, microcephaly, strabismus, and musculoskeletal anomalies. The two siblings homozygous for the p.(Arg163Trp) variant have severe symptoms including profound psychomotor retardation, intractable seizures, multiple bone fractures, scoliosis, loss of independent ambulation, and delayed myelination on brain MRI. Serum iron levels were significantly elevated in one individual. All tested individuals with PIGH deficiency had normal alkaline phosphatase and CD16, a GPI-anchored protein (GPI-AP), was found to be decreased by 60% on granulocytes from one individual. This study expands the PIGH deficiency phenotype range toward the severe end of the spectrum with the identification of a novel pathogenic variant.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.010
Threshold uncertainty score0.396

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.089
GPT teacher head0.359
Teacher spread0.270 · 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 teacher head, 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

Citations11
Published2020
Admission routes2
Has abstractyes

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