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Record W2534401479 · doi:10.1002/ajmg.a.38021

Implication of <i>LRRC4C</i> and <i>DPP6</i> in neurodevelopmental disorders

2016· article· en· W2534401479 on OpenAlexafffund
Gilles Maussion, Cristiana Cruceanu, Jill A. Rosenfeld, Scott C. Bell, Fabrice Jollant, Jin Szatkiewicz, Ryan L. Collins, Carrie Hanscom, Ilaria Kolobova, Nicolas Menjot de Champfleur, Ian Blumenthal, Colby Chiang, Vanessa Ota, Christina M. Hultman, Colm O’Dushlaine, Steve McCarroll, Martin Alda, Sébastien Jacquemont, Zehra Ordulu, Christian R. Marshall, Melissa T. Carter, Lisa G. Shaffer, Pamela Sklar, Santhosh Girirajan, Cynthia C. Morton, James F. Gusella, Gustavo Turecki, Dimitri J. Stavropoulos, Patrick F. Sullivan, Stephen W. Scherer, Michael E. Talkowski, Carl Ernst

Bibliographic record

VenueAmerican Journal of Medical Genetics Part A · 2016
Typearticle
Languageen
FieldNeuroscience
TopicAxon Guidance and Neuronal Signaling
Canadian institutionsHospital for Sick ChildrenUniversité de MontréalCentre Hospitalier Universitaire Sainte-JustineSickKids FoundationUniversity of TorontoDalhousie UniversityChildren's Hospital of Eastern OntarioMcGill UniversityDouglas Mental Health University Institute
FundersCanadian Institutes of Health ResearchNational Institute of General Medical SciencesNatural Sciences and Engineering Research Council of CanadaCanada Research ChairsScottish Rite Charitable Foundation of Canada
KeywordsProbandGeneticsAutismPhenotypeBiologyNeurodevelopmental disorderExonIntellectual disabilityGeneMutationMedicinePsychiatry

Abstract

fetched live from OpenAlex

We performed whole-genome sequencing on an individual from a family with variable psychiatric phenotypes that had a sensory processing disorder, apraxia, and autism. The proband harbored a maternally inherited balanced translocation (46,XY,t(11;14)(p12;p12)mat) that disrupted LRRC4C, a member of the highly specialized netrin G family of axon guidance molecules. The proband also inherited a paternally derived chromosomal inversion that disrupted DPP6, a potassium channel interacting protein. Copy Number (CN) analysis in 14,077 cases with neurodevelopmental disorders and 8,960 control subjects revealed that 60% of cases with exonic deletions in LRRC4C had a second clinically recognizable syndrome associated with variable clinical phenotypes, including 16p11.2, 1q44, and 2q33.1 CN syndromes, suggesting LRRC4C deletion variants may be modifiers of neurodevelopmental disorders. In vitro, functional assessments modeling patient deletions in LRRC4C suggest a negative regulatory role of these exons found in the untranslated region of LRRC4C, which has a single, terminal coding exon. These data suggest that the proband's autism may be due to the inheritance of disruptions in both DPP6 and LRRC4C, and may highlight the importance of the netrin G family and potassium channel interacting molecules in neurodevelopmental disorders. © 2016 Wiley Periodicals, Inc.

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: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.462
Threshold uncertainty score0.242

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 head0.017
GPT teacher head0.280
Teacher spread0.263 · 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 designBench or experimental
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

Citations54
Published2016
Admission routes2
Has abstractyes

Explore more

Same venueAmerican Journal of Medical Genetics Part ASame topicAxon Guidance and Neuronal SignalingFrench-language works237,207