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Record W3182556863 · doi:10.1038/s41436-021-01260-4

Biallelic variants in PCDHGC4 cause a novel neurodevelopmental syndrome with progressive microcephaly, seizures, and joint anomalies

2021· article· en· W3182556863 on OpenAlexafffund
Reza Maroofian, Büşranur Çavdarlı, Florence Riccardi, Michael Field, Siddharth Banka, Dalal Bubshait, Yun Li, Jozef Hertecant, Shahid Mahmood Baig, David A. Dyment, Stéphanie Efthymiou, Uzma Abdullah, Ehtisham Ul Haq Makhdoom, Zafar Ali, Tobias Scherf de Almeida, Florence Molinari, Cécile Mignon‐Ravix, B. Chabrol, Jayne Antony, Lesley C. Adès, Alistair T. Pagnamenta, Adam Jackson, Sofia Douzgou, John C. Ambrose, Prabhu Arumugam, Marta Bleda, C. R. Boustred, Helen Brittain, Mark J. Caulfield, G. C. Chan, Tom Fowler, Adam Giess, Angela Hamblin, Shirley Henderson, Tim Hubbard, R. Jackson, J. Louise Jones, Dalia Kasperavičiūtė, Melis Kayikci, Athanasios Kousathanas, L. Lahnstein, S. E. A. Leigh, I. U. S. Leong, Fabrice Lopez, F. Maleady-Crowe, Loukas Moutsianas, Michael Mueller, Nirupa Murugaesu, Anna C. Need, Peter O’Donovan, Christopher A. Odhams, Christine Patch, D. Perez-Gil, Mariana Buongermino Pereira, J. Pullinger, T. Rahim, Augusto Rendon, T. Rogers, K. Savage, K. Sawant, Richard H. Scott, Afshan Siddiq, A. Sieghart, Samuel C. Smith, Alona Sosinsky, Alexander Stuckey, M. Tanguy, Ellen Thomas, Simon R. Thompson, Arianna Tucci, Elizabeth T. Walsh, M. J. Welland, Eric O. Williams, Katarzyna Witkowska, S. M. Wood, Christian Beetz, Vasiliki Karageorgou, Barbara Vona, Abolfazl Rad, Jamshaid Mahmood Baig, Tipu Sultan, Javeria Raza Alvi, Shazia Maqbool, Fatima Rahman, Mehran Beiraghi Toosi, Farah Ashrafzadeh, Shima Imannezhad, Ehsan Ghayoor Karimiani, Yasra Sarwar, Sheraz Khan, Muhammad Jameel, Angelika A. Noegel, Birgit Budde, Janine Altmüller, Susanne Motameny, Wolfgang Höhne, Henry Houlden, Peter Nürnberg, Bernd Wollnik, Laurent Villard, Fowzan S. Alkuraya, Matthew Osmond, Muhammad Sajid Hussain, Gökhan Yigit

Bibliographic record

VenueGenetics in Medicine · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenomics and Rare Diseases
Canadian institutionsChildren's Hospital of Eastern OntarioUniversity of Ottawa
FundersCenter for Molecular Medicine Cologne, University of CologneMedizinischen Fakultät, Eberhard Karls Universität TübingenDepartment of Health and Social CareAtaxia UKMedical Research CouncilMinisterium für Wissenschaft, Forschung und Kunst Baden-WürttembergCanadian Institutes of Health ResearchHigher Education Commission, PakistanEberhard Karls Universität TübingenUniversität zu KölnEuropean CommissionWellcome TrustCancer Research UKUniversity College LondonGenome AlbertaDeutsche ForschungsgemeinschaftMuscular Dystrophy UKMuscular Dystrophy AssociationGenome British ColumbiaOntario Genomics InstituteGenome CanadaBrain Research UKGreat Ormond Street Hospital CharityNational Institute for Health and Care ResearchOntario Genomics
KeywordsMicrocephalyMissense mutationGeneticsExome sequencingNeurodevelopmental disorderIntellectual disabilityBiologyGlobal developmental delayIn silicoExomeDisease gene identificationGenetic heterogeneityLoss functionMutationGenePhenotype

Abstract

fetched live from OpenAlex

PURPOSE: We aimed to define a novel autosomal recessive neurodevelopmental disorder, characterize its clinical features, and identify the underlying genetic cause for this condition. METHODS: We performed a detailed clinical characterization of 19 individuals from nine unrelated, consanguineous families with a neurodevelopmental disorder. We used genome/exome sequencing approaches, linkage and cosegregation analyses to identify disease-causing variants, and we performed three-dimensional molecular in silico analysis to predict causality of variants where applicable. RESULTS: -binding affinity, which is essential for multimerization of the protein, whereas the third missense variant directly influenced the cis-dimerization interface of PCDHGC4. CONCLUSION: We show that biallelic variants in PCDHGC4 are causing a novel autosomal recessive neurodevelopmental disorder and link PCDHGC4 as a member of the clustered PCDH family to a Mendelian disorder in humans.

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 score0.787
Threshold uncertainty score0.626

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 head0.017
GPT teacher head0.248
Teacher spread0.231 · 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

Citations28
Published2021
Admission routes2
Has abstractyes

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