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Record W4323812720 · doi:10.1002/jbmr.4799

Al-Gazali Skeletal Dysplasia Constitutes the Lethal End of ADAMTSL2-Related Disorders

2020· article· en· W4323812720 on OpenAlexaff
Dominyka Batkovskyte, F. Ellis McKenzie, Fulya Taylan, Pelin Özlem Şimşek‐Kiper, Sarah M. Nikkel, Hirofumi Ohashi, Roger E. Stevenson, Thuong Ha, Denise P. Cavalcanti, Hiroyuki Miyahara, Steven A. Skinner, Miguel Ángel Aguirre, Zühal Akçören, Gülen Eda Ütine, Tillie Chiu, Kenji Shimizu, Anna Hammarsjö, Koray Boduroğlu, Hannah W. Moore, Raymond J. Louie, Peer Arts, Allie Merrihew, Milena Babic, Matilda R. Jackson, Nikos Papadogiannakis, Anna Lindstrand, Ann Nordgren, Christopher Barnett, Hamish S. Scott, Andrei S. Chagin, Gen Nishimura, Giedré Grigelioniené

Bibliographic record

VenueJournal of Bone and Mineral Research · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicConnective tissue disorders research
Canadian institutionsB.C. Women's Hospital & Health CentreUniversity of British Columbia
FundersNational Human Genome Research InstituteSällskapet BarnavårdScience for Life LaboratoryVetenskapsrådetNational Health and Medical Research CouncilAustralian Genomics Health AllianceStiftelsen Frimurare Barnhuset i StockholmKarolinska InstitutetBroad InstituteStiftelsen PromobiliaBertil Hållstens ForskningsstiftelseGenomic Health
KeywordsSanger sequencingDysplasiaMedicineCompound heterozygosityBrachydactylyMacrocephalyPathologyGeneticsShort staturePediatricsBiologyMutationGene

Abstract

fetched live from OpenAlex

Lethal short-limb skeletal dysplasia Al-Gazali type (OMIM %601356), also called dysplastic cortical hyperostosis, Al-Gazali type, is an ultra-rare disorder previously reported in only three unrelated individuals. The genetic etiology for Al-Gazali skeletal dysplasia has up until now been unknown. Through international collaborative efforts involving seven clinical centers worldwide, a cohort of nine patients with clinical and radiographic features consistent with short-limb skeletal dysplasia Al-Gazali type was collected. The affected individuals presented with moderate intrauterine growth restriction, relative macrocephaly, hypertrichosis, large anterior fontanelle, short neck, short and stiff limbs with small hands and feet, severe brachydactyly, and generalized bone sclerosis with mild platyspondyly. Biallelic disease-causing variants in ADAMTSL2 were detected using massively parallel sequencing (MPS) and Sanger sequencing techniques. Six individuals were compound heterozygous and one individual was homozygous for pathogenic variants in ADAMTSL2. In one of the families, pathogenic variants were detected in parental samples only. Overall, this study sheds light on the genetic cause of Al-Gazali skeletal dysplasia and identifies it as a semi-lethal part of the spectrum of ADAMTSL2-related disorders. Furthermore, we highlight the importance of meticulous analysis of the pseudogene region of ADAMTSL2 where disease-causing variants might be located. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

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)0.001
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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.756
Threshold uncertainty score0.300

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
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 integrity0.0000.001
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 head0.031
GPT teacher head0.342
Teacher spread0.310 · 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

Citations18
Published2020
Admission routes1
Has abstractyes

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