Constitutional genetics

Week of 6 October 2026

16 articles

Geno'X Veille — genox-veille.fr

Key takeaways this week

►Genome: randomized Belgian trial: GS 39.8% versus 30% for standard of care (p = 0.015), but the gap falls to 7.3% (p = 0.069) after correction.
►rWGS in inpatient paediatric neurology: 45.1% phenotype-concordant diagnoses (79/175), management changed in 65.9% of diagnosed cases.
►CDK19: 28 individuals and Drosophila models: constant speech delay, epilepsy in 67%, supportive functional evidence.
►PIGB: motor neuropathy with conduction blocks in 12 patients from 9 families, a new adult phenotype for the GPI pathway.
►SLC26A2: 115-patient cohort, severity score and a cis-acting complex allele modifying severity.
►Reanalysis in the 100,000 Genomes Project (Wales): yield doubled from 20.8% to 42.2%, RNA for variants of uncertain significance.

Category:

Filters··Min. score

16 articles of 16

Sort

Neurodevelopment

PubMed

A nationwide prospective randomized trial for diagnosing developmental disorders demonstrates genome sequencing outperforms standard of care.

Unexplained developmental disorders: genome sequencing versus standard of care

Neurodevelopment

Genome Med 2026· OctRead

Rapid WGS

PubMed

Rapid Whole-Genome Sequencing in Pediatric Neurology Inpatients.

Genetic diagnosis by rapid genome sequencing in paediatric neurology inpatients

Rapid WGS

JAMA Neurol 2026· OctRead

MYO5B

PubMed

Clinical Spectrum, Genetic Profile, and Genotype-Phenotype Correlations in Microvillus Inclusion Disease: A Systematic Review.

Microvillus inclusion disease (congenital enteropathy)

Am J Med Genet A 2026· OctRead

CDK19

PubMed

Identification of novel CDK19 variants and Drosophila-based in vivo functional evidence supporting pathogenicity in neurodevelopmental disorders.

NeurodevelopmentPhenotypic expansionFunctional SNV

Genet Med 2026· OctRead

PIGB

Autosomal recessivePubMed

Biallelic PIGB Variants Cause Motor Neuropathy with Conduction Blocks and Peripheral Nerve Hyperexcitability.

Motor neuropathy with conduction blocks and peripheral nerve hyperexcitability (GPI deficiency)

NeurologyPhenotypic expansionFunctional SNV

Ann Neurol 2026· SepRead

SLC26A2

Autosomal recessivePubMed

Delineating the Phenotypic Spectrum of SLC26A2-related Skeletal Dysplasias in a Cohort of 115 Patients: Evidence for a Novel Complex Allele Modifying Disease Severity.

WGS / DiagnosisFunctional SNV

Genet Med 2026· OctRead

WGS / Diagnosis

PubMed

Reanalysis of genomic data doubles the diagnostic yield for Welsh patients recruited to the UK 100,000 Genomes Project.

Undiagnosed rare diseases: genome reanalysis in the 100,000 Genomes Project (Wales)

WGS / DiagnosisVUS reclassified

Eur J Hum Genet 2026· SepRead

STXBP1

PubMed

Functional profiling of STXBP1 missense variants using a novel dual-readout fluorometric assay.

NeurodevelopmentFunctional SNVVUS reclassified

Epilepsia 2026· SepRead

CSMD2

Autosomal recessive et dominantmedRxiv

Haploinsufficiency, de novo and biallelic missense variants in CSMD2 are associated with neurodevelopmental disorders

NeurodevelopmentPhenotypic expansionFunctional SNV

medRxiv 2026· SepRead

Rapid WGS

medRxiv

Overcoming a diagnostic blindspot: Identifying balanced translocations in Mendelian rare disease cohorts

Balanced reciprocal translocations in Mendelian rare disease: detection from short-read genome sequencing

Rapid WGS

medRxiv 2026· OctRead

Familial cascade testing: direct contact of relatives with free testing

PubMed

CHARGE free cascade genetic testing: Effectiveness and implementation outcomes from a hybrid type I feasibility trial.

Familial cascade testing: direct contact of relatives with free testing

Genet Med 2026· OctRead

ADAMTS6

PubMed

Loss of function variants in ADAMTS6: a new connective tissue disorder with heart defect, aortic aneurysm and neurodevelopmental features.

Connective tissue disorder with heart defect, aortic aneurysm and neurodevelopmental features

Functional SNV

Genet Med 2026· OctRead

FADD

PubMed

Current review of pediatric Fas-associated death domain protein deficiency: expanding clinical and therapeutic perspectives.

FADD deficiency (inborn error of immunity) in children

Clin Exp Pediatr 2026· SepRead

Neurodevelopment

PubMed

Imputation of fluid intelligence scores reduces ascertainment bias and increases power for analyses of common and rare variants.

Genetics of fluid intelligence and neurodevelopmental conditions (UK Biobank)

Neurodevelopment

Nat Genet 2026· OctRead

ECHS1

Autosomal recessivePubMed

Short-chain enoyl-CoA hydratase deficiency: a systematic review of clinical spectrum, genotype-phenotype correlations and survival predictors.

Short-chain enoyl-CoA hydratase (SCEH) deficiency (ECHS1 gene)

Neurogenetics 2026· OctRead

Prenatal

PubMed

Integrated Molecular Autopsy in a Highly Consanguineous Perinatal Cohort With Severe Malformations and Strong Genetic Susceptibility.

Severe perinatal malformations: integrated molecular autopsy in a consanguineous population

PrenatalPrenatal application

Prenat Diagn 2026· OctRead

References and sources

Unexplained developmental disorders: genome sequencing versus standard of care. Genome Med 2026. PMID 42830293. Score 8/10. https://pubmed.ncbi.nlm.nih.gov/42830293/
Genetic diagnosis by rapid genome sequencing in paediatric neurology inpatients. JAMA Neurol 2026. PMID 42832236. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42832236/
MYO5B — Microvillus inclusion disease (congenital enteropathy). Am J Med Genet A 2026. PMID 42834355. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42834355/
CDK19 — CDK19-related neurodevelopmental disorder. Genet Med 2026. PMID 42820262. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42820262/
PIGB — Motor neuropathy with conduction blocks and peripheral nerve hyperexcitability (GPI deficiency). Ann Neurol 2026. PMID 42813498. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42813498/
SLC26A2 — SLC26A2-related skeletal dysplasias (from recessive multiple epiphyseal dysplasia to atelosteogenesis type 2). Genet Med 2026. PMID 42831386. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42831386/
Undiagnosed rare diseases: genome reanalysis in the 100,000 Genomes Project (Wales). Eur J Hum Genet 2026. PMID 42806038. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42806038/
STXBP1 — STXBP1-related disorders (epileptic encephalopathy and neurodevelopmental disorder). Epilepsia 2026. PMID 42811883. Score 6/10. https://pubmed.ncbi.nlm.nih.gov/42811883/
CSMD2 — CSMD2-related neurodevelopmental disorder. medRxiv 2026. doi:10.64898/2026.09.24.26361611. Score 6/10. https://www.medrxiv.org/content/10.64898/2026.09.24.26361611v1
Balanced reciprocal translocations in Mendelian rare disease: detection from short-read genome sequencing. medRxiv 2026. doi:10.64898/2026.09.30.26363717. Score 6/10. https://www.medrxiv.org/content/10.64898/2026.09.30.26363717v1
Familial cascade testing: direct contact of relatives with free testing. Genet Med 2026. PMID 42820263. Score 6/10. https://pubmed.ncbi.nlm.nih.gov/42820263/
ADAMTS6 — Connective tissue disorder with heart defect, aortic aneurysm and neurodevelopmental features. Genet Med 2026. PMID 42829835. Score 6/10. https://pubmed.ncbi.nlm.nih.gov/42829835/
FADD — FADD deficiency (inborn error of immunity) in children. Clin Exp Pediatr 2026. PMID 42722396. Score 6/10. https://pubmed.ncbi.nlm.nih.gov/42722396/
Genetics of fluid intelligence and neurodevelopmental conditions (UK Biobank). Nat Genet 2026. PMID 42834203. Score 6/10. https://pubmed.ncbi.nlm.nih.gov/42834203/
ECHS1 — Short-chain enoyl-CoA hydratase (SCEH) deficiency (ECHS1 gene). Neurogenetics 2026. PMID 42825840. Score 6/10. https://pubmed.ncbi.nlm.nih.gov/42825840/
Severe perinatal malformations: integrated molecular autopsy in a consanguineous population. Prenat Diagn 2026. PMID 42822536. Score 5/10. https://pubmed.ncbi.nlm.nih.gov/42822536/

Previous week

29 September 2026