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Record W2100469122 · doi:10.1002/ajmg.a.35558

A novel nonsense <i>CDK5RAP2</i> mutation in a Somali child with primary microcephaly and sensorineural hearing loss

2012· article· en· W2100469122 on OpenAlexaff
Alistair T. Pagnamenta, Jennie Murray, Grace Yoon, Elham Sadighi Akha, Victoria Harrison, Louise S. Bicknell, Kaseem Ajilogba, Helen Stewart, Usha Kini, Jenny C. Taylor, David A. Keays, Andrew P. Jackson, Samantha J.L. Knight

Bibliographic record

VenueAmerican Journal of Medical Genetics Part A · 2012
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetics and Neurodevelopmental Disorders
Canadian institutionsSickKids FoundationHospital for Sick ChildrenUniversity of Toronto
FundersAustrian Science FundNational Institute for Health and Care ResearchWellcome Trust
KeywordsMicrocephalySensorineural hearing lossGeneticsHearing lossLoss of heterozygosityBiologyNonsense mutationMutationCompound heterozygosityConsanguinityGlobal developmental delayMedicineAlleleAudiologyPhenotypeGeneMissense mutation

Abstract

fetched live from OpenAlex

Primary microcephaly is a genetically heterogeneous condition characterized by reduced head circumference (-3 SDS or more) and mild-to-moderate learning disability. Here, we describe clinical and molecular investigations of a microcephalic child with sensorineural hearing loss. Although consanguinity was unreported initially, detection of 13.7 Mb of copy neutral loss of heterozygosity (cnLOH) on chromosome 9 implicated the CDK5RAP2 gene. Targeted sequencing identified a homozygous E234X mutation, only the third mutation to be described in CDK5RAP2, the first in an individual of non-Pakistani descent. Sensorineural hearing loss is not generally considered to be consistent with autosomal recessive microcephaly and therefore it seems likely that the deafness in this individual is caused by the co-occurrence of a further gene mutation, independent of CDK5RAP2. Nevertheless, further detailed clinical descriptions of rare CDK5RAP2 patients, including hearing assessments will be needed to resolve fully the phenotypic range associated with mutations in this gene. This study also highlights the utility of SNP-array testing to guide disease gene identification where an autosomal recessive condition is plausible.

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 score0.624
Threshold uncertainty score0.541

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 head0.008
GPT teacher head0.239
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

Citations41
Published2012
Admission routes1
Has abstractyes

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Same venueAmerican Journal of Medical Genetics Part ASame topicGenetics and Neurodevelopmental DisordersFrench-language works237,207