MétaCan
Menu
Back to cohort
Record W2920511853 · doi:10.2298/abs181227009s

Phenotypic expression and founder effect of PANK2 c.1583C>T (p.T528M) mutation in Serbian pantothenate kinase-associated neurodegeneration patients

2019· article· en· W2920511853 on OpenAlexaff
Marina Svetel, Monika Hartig, Dragana Cvetković, Cyrielle Beaubois, Jasmina Maksić, Ivana Novaković, Maja Krajinović, Vladimir Kostić

Bibliographic record

VenueArchives of Biological Sciences · 2019
Typearticle
Languageen
FieldNeuroscience
TopicNeurological diseases and metabolism
Canadian institutionsUniversité de MontréalCentre Hospitalier Universitaire Sainte-Justine
FundersMinistarstvo Prosvete, Nauke i Tehnološkog Razvoja
KeywordsGeneticsBiologyHaplotypeNeurodegenerationParkinsonismFounder effectMutationSingle-nucleotide polymorphismCompound heterozygosityPhenotypeGeneAlleleGenotypeMedicinePathology

Abstract

fetched live from OpenAlex

Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive disorder characterized by dystonia, parkinsonism, cognitive and visual impairment, and iron accumulation in the brain. Many cases of PKAN result from mutations in the PANK2 gene that encodes pantothenate kinase 2, a key regulatory enzyme in the biosynthesis of coenzyme A. We previously detected six Serbian patients with clinically suggestive PKAN, all of whom had PANK2 c.1583C>T (p.T528M) mutation either in the homozygous or in the heterozygous state. In this study we explored the phenotypic expression and a possible founder effect of this substitution. We performed the analysis of linkage disequilibrium (LD) and organization in haplotypes of 23 single nucleotide polymorphisms (SNPs) adjacent to the PANK2 gene in all of the six patients and their parents, as well as in control healthy child-parents trios. The age of PANK2 c.1583C>T mutation was determined using the r2 degeneration method. Clinical findings in our patients were markedly similar. Different LD structures between patients and controls is revealed, and PANK2 c.1583T allele was significantly associated with a particular haplotype. The age of PANK2 c.1583C>T mutation was estimated to be about 15 generations. Our results suggest that PANK2 c.1583C>T in Serbian PKAN patients represents a founder mutation descended from one common ancestor.

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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.620
Threshold uncertainty score0.301

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 studies0.0000.001
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 head0.022
GPT teacher head0.256
Teacher spread0.234 · 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

Citations1
Published2019
Admission routes1
Has abstractyes

Explore more

Same venueArchives of Biological SciencesSame topicNeurological diseases and metabolismFrench-language works237,207