Constitutional genetics

Week of 8 September 2026

16 articles

Geno'X Veille — genox-veille.fr

Key takeaways this week

►ZNF536 — 21 individuals, 12 de novo variants and a concordant knock-in mouse: a new neurodevelopmental disorder gene with behavioural dysregulation.
►LDLR — prime editing screen of 5,184 coding variants: 322 variants of uncertain significance reach reclassification thresholds.
►CHD1 — androgens modulate penetrance in Pilarowski-Bjornsson syndrome, demonstrated by orchiectomy and testosterone in mice.
►HBB — the complete T2T reference cuts structural variant calls across the beta-globin cluster by 70% in 40 African patients with sickle cell disease.
►MAP3K7 — four convergent lines of evidence establish loss of function as a cause of apparently isolated dilated cardiomyopathy.
►Prenatal exome — 44% diagnostic rate in nonimmune hydrops fetalis after a negative standard workup, versus 7% incremental yield for genome sequencing.

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Autosomal dominantPubMed

Monoallelic loss-of-function variants in ZNF536 are associated with a neurodevelopmental disorder with prominent behavioral features

Neurodevelopmental disorder with prominent behavioral features

NeurodevelopmentNew geneFunctional SNV

Am J Hum Genet 2026· SepRead

Autosomal dominantPubMed

LDLR Variant Classification Through Activity-Normalized Prime Editing Screening

Familial hypercholesterolemia

VUS reclassifiedFunctional SNV

Circulation 2026· SepRead

Autosomal dominantPubMed

Androgens mediate sexual dimorphism in Pilarowski-Bjornsson syndrome

Pilarowski-Bjornsson syndrome

NeurodevelopmentNew mechanismFunctional SNV

Am J Hum Genet 2026· SepRead

Neurodevelopment

Whole-exome sequencing in individuals with obsessive-compulsive disorder and chronic tic disorders identifies 36 large-effect risk genes

Obsessive-compulsive disorder and chronic tic disorders

NeurodevelopmentNew gene

Nat Neurosci 2026· SepRead

Thoracic aortic disease: prognostic role of gene variants and polygenic risk scores

Thoracic aortic aneurysm and dissection

Eur Heart J 2026· SepRead

Hypertrophic cardiomyopathy: a genome-wide association meta-analysis and polygenic risk score

Hypertrophic cardiomyopathy

J Med Genet 2026· SepRead

Récessif lié à l'XPubMed

Development of RS1-specific ACMG/AMP variant classification criteria with pilot variant curation

X-linked retinoschisis

VUS reclassified

Hum Genet 2026· SepRead

High Diagnosis Rate for Nonimmune Hydrops Fetalis With Prenatal Clinical Genome: Expanded Results From the Hydrops-Yielding Diagnostic Results of Prenatal Sequencing (HYDROPS) Study

Nonimmune hydrops fetalis

PrenatalPrenatal application

Am J Med Genet A 2026· AugRead

Autosomal recessivePubMed

Long-read Sequences Mapped to a Complete Reference Genome Uncover Uncaptured Structural Variants across the Beta-globin Cluster in Africans with Sickle Cell Disease

Sickle cell disease

Long-read WGSLong-read sequencing

HGG Adv 2026· SepRead

Why atypical findings matter: Follow up testing finds diagnostic results related to cfDNA screen

Atypical prenatal cell-free DNA screening results

PrenatalPrenatal application

Genet Med 2026· SepRead

Autosomal dominantmedRxiv

MAP3K7 Loss of Function Causes Dilated Cardiomyopathy

Dilated cardiomyopathy

CardiologyPhenotypic expansionFunctional SNV

medRxiv 2026· SepRead

Autosomal recessivePubMed

Phenotypic and transcriptomic characterization of biallelic RNU2-2 developmental and epileptic encephalopathy

Developmental and epileptic encephalopathy

Metabolism / EpilepsyFunctional SNV

Epilepsia 2026· SepRead

Rapid Genomic Testing: A Study of Institutional Utilization and Outcomes

Rapid genomic testing in critically ill patients

Am J Med Genet A 2026· SepRead

Autosomal dominant ou autosomal recessivePubMed

The Evaluation of Molecular Genetics and Clinical Manifestations in Patients With LZTR1-Associated Noonan Syndrome: A Retrospective Chart Review and Review of Literature

Noonan syndrome

CardiologyPhenotypic expansion

Am J Med Genet A 2026· SepRead

Familial, neuropathological and cellular analysis identify ARPP21 as a major amyotrophic lateral sclerosis associated gene in French cohorts

Amyotrophic lateral sclerosis

Recurrent variantFunctional SNV

Acta Neuropathol 2026· SepRead

Autosomal recessivePubMed

A novel deep intronic EIF2AK3 variant disrupts splicing and causes Wolcott-Rallison syndrome

Wolcott-Rallison syndrome

Deep intronic variantFunctional SNV

Diabet Med 2026· SepRead

References and sources

ZNF536 — Neurodevelopmental disorder with prominent behavioral features. Am J Hum Genet 2026. PMID 42697193. Score 10/10. https://pubmed.ncbi.nlm.nih.gov/42697193/
LDLR — Familial hypercholesterolemia. Circulation 2026. PMID 42677454. Score 9/10. https://pubmed.ncbi.nlm.nih.gov/42677454/
Obsessive-compulsive disorder and chronic tic disorders. Nat Neurosci 2026. PMID 42680906. Score 8/10. https://pubmed.ncbi.nlm.nih.gov/42680906/
Thoracic aortic aneurysm and dissection. Eur Heart J 2026. PMID 42678067. Score 8/10. https://pubmed.ncbi.nlm.nih.gov/42678067/
Hypertrophic cardiomyopathy. J Med Genet 2026. PMID 42697718. Score 8/10. https://pubmed.ncbi.nlm.nih.gov/42697718/
HBB — Sickle cell disease. HGG Adv 2026. PMID 42693638. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42693638/
CHD1 — Pilarowski-Bjornsson syndrome. Am J Hum Genet 2026. PMID 42692004. Score 9/10. https://pubmed.ncbi.nlm.nih.gov/42692004/
RS1 — X-linked retinoschisis. Hum Genet 2026. PMID 42696042. Score 8/10. https://pubmed.ncbi.nlm.nih.gov/42696042/
Atypical prenatal cell-free DNA screening results. Genet Med 2026. PMID 42703844. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42703844/
MAP3K7 — Dilated cardiomyopathy. medRxiv 2026. doi:10.64898/2026.09.02.26361780. Score 7/10. https://www.medrxiv.org/content/10.64898/2026.09.02.26361780v1
ARPP21 — Amyotrophic lateral sclerosis. Acta Neuropathol 2026. PMID 42696048. Score 6/10. https://pubmed.ncbi.nlm.nih.gov/42696048/
RNU2-2 — Developmental and epileptic encephalopathy. Epilepsia 2026. PMID 42678714. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42678714/
Nonimmune hydrops fetalis. Am J Med Genet A 2026. PMID 42624826. Score 8/10. https://onlinelibrary.wiley.com/doi/10.1002/ajmg.a.70265?af=R
EIF2AK3 — Wolcott-Rallison syndrome. Diabet Med 2026. PMID 42689758. Score 5/10. https://pubmed.ncbi.nlm.nih.gov/42689758/
Rapid genomic testing in critically ill patients. Am J Med Genet A 2026. PMID 42677465. Score 7/10. https://onlinelibrary.wiley.com/doi/10.1002/ajmg.a.70295?af=R
LZTR1 — Noonan syndrome. Am J Med Genet A 2026. PMID 42687096. Score 7/10. https://onlinelibrary.wiley.com/doi/10.1002/ajmg.a.70297?af=R

1 September 2026

15 September 2026