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Record W4415976494 · doi:10.1101/2025.11.04.25339178

Recessive genomic and phenotypic variation in consanguineous families with cerebral palsy

2025· preprint· en· W4415976494 on OpenAlexaff
Pritha Bisarad, Yung-Chun Wang, Peter T. Skidmore, Carolina I. Galaz-Montoya, Sara A. Lewis, Bader Alhaddad, Nahyun Kong, Dominic Julian, Helen Magee, Tyler N. Kruer, Yuhan Xie, Wangjie Zheng, Boyang Li, Fatemeh Vand Rajabpour, James Liu, Anjali Revanur, Khadijah Bakur, Saghar Ghasemi Firouzabadi, Sarina Sharbatkhori, Abbas Tafakhori, Ehsan Taghiabadi, Ermia Nezaminargabad, Shohreh Vosoogh, Javad Jamshidi, Serajaddin Arefnia, Seyed Ahmad Hosseini, Alireza Khajehmirzaei, Faezeh Jamali, Azadeh Ahmadifard, Hamidreza Khodadadi, P. Daneshmand, Saeed Bohlega, Sateesh Maddirevula, Seba Nadeef, Mustafa A. Salih, Inaam N. Mohmed, Heinrich Sticht, Sara Peres Morias, Joana Damásio, Mariana Santos, José Leal Loureiro, Rita Rodrigues, Giovanni Stévanin, Mehdi Benkirane, Benjamin Dauriat, Nicholas Head, Júlia Baptista, Saeid Shahhosseini, Farhan Mohammad, Hongyu Zhao, Sergio Padilla‐Lopez, Fowzan S. Alkuraya, Somayeh Bakhtiari, Michael C. Kruer, Sheng Chih Jin, Hossein Darvish

Bibliographic record

VenuemedRxiv · 2025
Typepreprint
Languageen
FieldNeuroscience
TopicHereditary Neurological Disorders
Canadian institutionsArtificial Intelligence in Medicine (Canada)
FundersNational Institutes of HealthCerebral Palsy AllianceCerebral Palsy Alliance Research FoundationChildren's Discovery Institute
KeywordsConsanguinityPhenotypeMendelian inheritanceGeneMultifactorial InheritanceAlleleGenetic variationInheritance (genetic algorithm)

Abstract

fetched live from OpenAlex

ABSTRACT Cerebral palsy (CP) is a neurodevelopmental disorder of motor function, with genetic etiologies, particularly de novo variants, identified in approximately one-third of cases. The contribution of consanguinity – long-recognized as a CP risk factor – has remained undefined. Here, we report findings from 188 primarily consanguineous Middle Eastern families with CP and identified putative causative genes in nearly three-quarters. The majority demonstrated recessive inheritance, although multi-level consanguinity and multilocus pathogenic variants complicated Mendelian assortment analyses. We identified 110 known CP-associated genes – five with phenotypic expansions and three others exhibiting new recessive inheritance patterns – and 24 novel candidates. We characterized ten candidates as high-confidence based on independent replication and protein modeling. We experimentally validated a role for SUCO variants in CP and newly identified a role for mid-gestational migrating excitatory neurons in the disorder. These findings highlight new genes, pathways, and phenotypes that reveal striking genomic diversity in CP.

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)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.145
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
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 integrity0.0000.001
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 head0.023
GPT teacher head0.251
Teacher spread0.228 · 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.

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

Citations0
Published2025
Admission routes1
Has abstractyes

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