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Record W2169987539 · doi:10.1002/ajmg.a.35202

Phenotypic variability in hyperphosphatasia with seizures and neurologic deficit (Mabry syndrome)

2012· article· en· W2169987539 on OpenAlexafffund
Miles D. Thompson, Tony Roscioli, Carlo Marcelis, Marjan M. Nezarati, Irene Stolte‐Dijkstra, Frances J. Sharom, Pei‐Hua Lu, Elizabeth Sweeney, Peter N. Robinson, Peter Krawitz, Helger G. Yntema, Danielle M. Andrade, Han G. Brunner, David E.C. Cole

Bibliographic record

VenueAmerican Journal of Medical Genetics Part A · 2012
Typearticle
Languageen
FieldMedicine
TopicGlycogen Storage Diseases and Myoclonus
Canadian institutionsHealth Sciences CentreHospital for Sick ChildrenUniversity of GuelphSunnybrook Health Science CentreNorth York General HospitalToronto Western HospitalUniversity of Toronto
FundersNational Health and Medical Research CouncilNatural Sciences and Engineering Research Council of Canada
KeywordsCompound heterozygosityExonMutationPhenotypeGeneticsHeterozygote advantageEndocrinologyBiologyInternal medicineGeneMedicineAllele

Abstract

fetched live from OpenAlex

Hyperphosphatasia with neurologic deficit (Mabry syndrome) was first described in a single family (OMIM#239300) by Mabry et al. [1970]. Although considered rare at the time, more than 20 individuals with the triad of developmental disability, seizures, and hyperphosphatasia have been identified world-wide. The 1-6 mannosyltransferase 2, phosphatidylinositol glycan V (PIGV) gene has been found to be disrupted in some patients with the additional feature of brachytelephalangy. In the present report we identify three patients compound homozygous for PIGV mutations. Two siblings were found to be compound heterozygotes for c.467G > A and c.494C > A in exon 3 of PIGV (the c.494C > A PIGV variant is novel). A third patient with similar phenotype, was a compound heterozygote for the known c.1022C > A/c.1022C > T (p.Ala341Glu/p.Ala341Val) mutation. This patient was also noted to have lysosomal storage in cultured fibroblasts. In contrast, the fourth patient who had no apparent hand abnormality, was found to be heterozygous for a previously unclassified c.1369C > T mutation in exon 4 of the PIGV gene, resulting in a p.Leu457Phe substitution in the catalytic domain of the enzyme. Unless this variant has a dominant negative effect, however, it seems likely that another GPI biosynthesis gene variant may contribute to the disorder, possibly through digenic inheritance. Since slightly fewer than half of the nine cases presented in this report and our previous report [Thompson et al., 2010] have PIGV mutations, we suggest that other genes critical to GPI anchor biosynthesis are likely to be disrupted in some patients.

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)0.001
metaresearch head score (Gemma)0.000
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 score0.153
Threshold uncertainty score0.421

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
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 head0.010
GPT teacher head0.261
Teacher spread0.251 · 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

Citations46
Published2012
Admission routes2
Has abstractyes

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