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Record W4220665137 · doi:10.1016/j.gim.2022.02.013

SOX11 variants cause a neurodevelopmental disorder with infrequent ocular malformations and hypogonadotropic hypogonadism and with distinct DNA methylation profile

2022· article· en· W4220665137 on OpenAlexafffund
Reem Al‐Jawahiri, Aidin Foroutan, Jennifer Kerkhof, Haley McConkey, Michael A. Levy, Sadegheh Haghshenas, Kathleen Rooney, Jasmin E. Turner, Debbie Shears, Muriel Holder, Henrietta Lefroy, Bruce Castle, Linda M. Reis, Elena V. Semina, Deborah A. Nickerson, Michael J. Bamshad, Suzanne M. Leal, Katherine Lachlan, Kate Chandler, Thomas Wright, Jill Clayton‐Smith, Franziska Phan Hug, Nelly Pitteloud, Lucia Bartoloni, Sabine Hoffjan, Soo‐Mi Park, Ajay Thankamony, Melissa Lees, Emma Wakeling, Swati Naik, Britta Hanker, Katta M. Girisha, Emanuele Agolini, Giuseppe Zampino, Alban Ziegler, Marine Tessarech, Boris Keren, Alexandra Afenjar, Christiane Zweier, André Reis, Thomas Smol, Yoshinori Tsurusaki, Nobuhiko Okamoto, Futoshi Sekiguchi, Naomi Tsuchida, Naomichi Matsumoto, Ikuyo Kou, Yoshiro Yonezawa, Shiro Ikegawa, Bert Callewaert, Megan Freeth, John C. Ambrose, Prabhu Arumugam, R. Bevers, Marta Bleda, C. R. Boustred, Helen Brittain, Mark J. Caulfield, G. C. Chan, Greg Elgar, Tom Fowler, Adam Giess, Angela Hamblin, Shirley Henderson, Tim Hubbard, Robert B. Jackson, J. Louise Jones, Dalia Kasperavičiūtė, Melis Kayikci, Athanasios Kousathanas, L. Lahnstein, S. E. A. Leigh, I. U. S. Leong, Javier Ferreiros, FionaMaleady-Crowe, Meriel McEntagart, Federico Minneci, Loukas Moutsianas, Michael Mueller, Nirupa Murugaesu, Anna C. Need, Peter O’Donovan, Chris A. Odhams, Christine Patch, Mariana Buongermino Pereira, D. Perez-Gil, J. Pullinger, TahrimaRahim, Augusto Rendon, TimRogers, K. Savage, Kushmita Sawant, Richard H. Scott, Afshan Siddiq, A. Sieghart, Samuel C. Smith, Alona Sosinsky, Alexander Stuckey, M. Tanguy, Ana Lisa Taylor Tavares, Ellen Thomas, Simon R. Thompson, Arianna Tucci, M. J. Welland, Eleanor Williams, Katarzyna Witkowska, S. M. Wood, Lotte Kleinendorst, Alan C. Donaldson, Mariëlle Alders, Anne De Paepe, Bekim Sadiković, Alisdair McNeill

Bibliographic record

VenueGenetics in Medicine · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicOcular Disorders and Treatments
Canadian institutionsLondon Health Sciences CentreWestern University
FundersNational Eye InstituteNational Heart, Lung, and Blood InstituteCenter for Mendelian Genomics, University of WashingtonMedical Research CouncilDepartment of Health and Social CareNational Institutes of HealthNIH Office of the DirectorCancer Research UKWaterloo FoundationNational Human Genome Research InstituteWellcome TrustJapan Agency for Medical Research and DevelopmentNational Institute for Health and Care ResearchGenome CanadaUniversity of Washington
KeywordsDNA methylationExome sequencingPhenotypeHypogonadotropic hypogonadismGeneticsExomeBioinformaticsBiologyMedicineNeurodevelopmental disorderComputational biologyGeneInternal medicineGene expression

Abstract

fetched live from OpenAlex

PURPOSE: This study aimed to undertake a multidisciplinary characterization of the phenotype associated with SOX11 variants. METHODS: Individuals with protein altering variants in SOX11 were identified through exome and genome sequencing and international data sharing. Deep clinical phenotyping was undertaken by referring clinicians. Blood DNA methylation was assessed using Infinium MethylationEPIC array. The expression pattern of SOX11 in developing human brain was defined using RNAscope. RESULTS: We reported 38 new patients with SOX11 variants. Idiopathic hypogonadotropic hypogonadism was confirmed as a feature of SOX11 syndrome. A distinctive pattern of blood DNA methylation was identified in SOX11 syndrome, separating SOX11 syndrome from other BAFopathies. CONCLUSION: SOX11 syndrome is a distinct clinical entity with characteristic clinical features and episignature differentiating it from BAFopathies.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.008
GPT teacher head0.225
Teacher spread0.217 · 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 source (direct Gemma or distilled Codex), 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

Citations36
Published2022
Admission routes2
Has abstractyes

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