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Record W3100188494 · doi:10.1038/s41436-020-00993-y

Defining the genotypic and phenotypic spectrum of X-linked MSL3-related disorder

2020· article· en· W3100188494 on OpenAlexaff
Theresa Brunet, Kirsty McWalter, Katharina Mayerhanser, Grace M. Anbouba, Amy Armstrong‐Javors, Ingrid Bader, Evan H. Baugh, Amber Begtrup, Caleb Bupp, Bert Callewaert, Anna Cereda, Margot A. Cousin, Juan Carlos Del Rey Jimenez, Laurie Demmer, Nikita R. Dsouza, Nicole Fleischer, Ralitza H. Gavrilova, Sumedha Ghate, Elisabeth Graf, Andrew Green, Sarah R. Green, Maria Iascone, Ameni Kdissa, Dirk Klee, Eric W. Klee, Emily Lancaster, Kristin Lindstrom, Johannes A. Mayr, Meriel McEntagart, Naomi Meeks, Dana Mittag, Harrison Moore, Anne K. Olsen, Damara Ortiz, Gretchen Parsons, Loren D.M. Peña, Richard Person, Sumit Punj, Gonzalo Alonso Ramos-Rivera, María J. Guillen Sacoto, G. Bradley Schaefer, Rhonda E. Schnur, Tiana M. Scott, Daryl A. Scott, Carolyn R. Serbinski, Vandana Shashi, Victoria Mok Siu, Barbro Stadheim, Jennifer A. Sullivan, Jana Švantnerová, Lea Velsher, David S. Wargowski, Ingrid M. Wentzensen, Dagmar Wieczorek, Juliane Winkelmann, Patrick Yap, Michael Zech, Michael T. Zimmermann, Thomas Meitinger, Felix Distelmaier, Matias Wagner

Bibliographic record

VenueGenetics in Medicine · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCongenital heart defects research
Canadian institutionsNorth York General HospitalWestern University
FundersVlaamse regeringDeutsche Forschungsgemeinschaft
KeywordsAutism spectrum disorderGeneticsMissense mutationExonNonsenseIntellectual disabilityFrameshift mutationMacrocephalyBiologyExome sequencingGenotypeAllelic heterogeneityGenotype-phenotype distinctionPhenotypeAutismMedicineGenePsychiatry

Abstract

fetched live from OpenAlex

PURPOSE: We sought to delineate the genotypic and phenotypic spectrum of female and male individuals with X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome). METHODS: Twenty-five individuals (15 males, 10 females) with causative variants in MSL3 were ascertained through exome or genome sequencing at ten different sequencing centers. RESULTS: We identified multiple variant types in MSL3 (ten nonsense, six frameshift, four splice site, three missense, one in-frame-deletion, one multi-exon deletion), most proven to be de novo, and clustering in the terminal eight exons suggesting that truncating variants in the first five exons might be compensated by an alternative MSL3 transcript. Three-dimensional modeling of missense and splice variants indicated that these have a deleterious effect. The main clinical findings comprised developmental delay and intellectual disability ranging from mild to severe. Autism spectrum disorder, muscle tone abnormalities, and macrocephaly were common as well as hearing impairment and gastrointestinal problems. Hypoplasia of the cerebellar vermis emerged as a consistent magnetic resonance image (MRI) finding. Females and males were equally affected. Using facial analysis technology, a recognizable facial gestalt was determined. CONCLUSION: Our aggregated data illustrate the genotypic and phenotypic spectrum of X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome). Our cohort improves the understanding of disease related morbidity and allows us to propose detailed surveillance guidelines for affected individuals.

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)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.554
Threshold uncertainty score0.340

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
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 head0.014
GPT teacher head0.285
Teacher spread0.271 · 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

Citations14
Published2020
Admission routes1
Has abstractyes

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