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Record W2767307071 · doi:10.1038/s41598-017-15442-1

Novel KIAA0753 mutations extend the phenotype of skeletal ciliopathies

2017· article· en· W2767307071 on OpenAlexaff
Anna Hammarsjö, Z. Wang, Raquel Vaz, Fulya Taylan, Maryam Sedghi, Katta M. Girisha, David Chitayat, Patrick Shannon, Ruth Godoy, Kalpana Gowrishankar, Anna Lindstrand, Jafar Nasiri, Mojtaba Baktashian, Phillip T. Newton, Long Guo, Wolfgang Hofmeister, Maria Pettersson, Andrei S. Chagin, Gen Nishimura, Yan Li, Naomichi Matsumoto, Ann Nordgren, Noriko Miyake, Giedré Grigelioniené, Shiro Ikegawa

Bibliographic record

VenueScientific Reports · 2017
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic and Kidney Cyst Diseases
Canadian institutionsHospital for Sick ChildrenUniversity of TorontoSickKids FoundationMount Sinai Hospital
FundersUppsala Multidisciplinary Center for Advanced Computational ScienceJapan Society for the Promotion of ScienceSällskapet BarnavårdScience for Life LaboratoryNational Key Research and Development Program of ChinaStockholms Läns LandstingRIKENKarolinska InstitutetJapan Agency for Medical Research and Development
KeywordsCiliopathiesJoubert syndromeBiologyNonsense mutationCiliopathyFrameshift mutationPenetranceGeneticsPhenotypeZebrafishDysplasiaMutationPathologyCiliumMedicineGeneMissense mutation

Abstract

fetched live from OpenAlex

The skeletal ciliopathies are a heterogeneous group of disorders with a significant clinical and genetic variability and the main clinical features are thoracic hypoplasia and short tubular bones. To date, 25 genes have been identified in association with skeletal ciliopathies. Mutations in the KIAA0753 gene have recently been associated with Joubert syndrome (JBTS) and orofaciodigital (OFD) syndrome. We report biallelic pathogenic variants in KIAA0753 in four patients with short-rib type skeletal dysplasia. The manifestations in our patients are variable and ranging from fetal lethal to viable and moderate skeletal dysplasia with narrow thorax and abnormal metaphyses. We demonstrate that KIAA0753 is expressed in normal fetal human growth plate and show that the affected fetus, with a compound heterozygous frameshift and a nonsense mutation in KIAA0753, has an abnormal proliferative zone and a broad hypertrophic zone. The importance of KIAA0753 for normal skeletal development is further confirmed by our findings that zebrafish embryos homozygous for a nonsense mutation in kiaa0753 display altered cartilage patterning.

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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.001
Research integrity0.0010.000
Insufficient payload (model declined to judge)0.0020.001

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 head0.013
GPT teacher head0.264
Teacher spread0.250 · 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
Published2017
Admission routes1
Has abstractyes

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