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Constitutional genetics

Week of 4 August 2026

16 articles

Geno'X Veille — genox-veille.fr

Key takeaways this week

►ARID1B — a 160-CpG episignature allowed classification of 14 additional variants, but does not separate ARID1B from SMARCB1.
►G6PD deficiency — BabyDetect genomic screening identified 94 newborns carrying pathogenic variants, including 17 missed by routine biochemical screening.
►21-hydroxylase deficiency — 71% of never-treated classic patients had no adrenal crisis, while a basal 17-OHP cut-off of 170 ng/dL (AUC 0.98) is enough to screen for non-classic forms without stimulation testing.
►Cardiomyopathies — among 469,671 UK Biobank participants, carriers of rare predicted deleterious variants had a higher risk of sudden cardiac death or malignant ventricular arrhythmia (HR 1.28; 95% CI 1.11-1.48) despite 1% penetrance.
►EXOSC6 — the ninth and final RNA exosome core subunit joins the exosomopathies: the family is now complete.
►Familial hypercholesterolaemia — in carriers, the cardiovascular signature activates before the first coronary event (OR 1.63), across more than 683,000 individuals from three biobanks.

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Autosomal dominantPubMed

Characterizing ARID1B-related disorders and variants of uncertain significance using DNA methylation.

ARID1B-related neurodevelopmental disorders

NeurodevelopmentVUS reclassified

Eur J Hum Genet 2026· JulRead

Autosomal recessivePubMed

Survival without treatment of patients with classic and non-classic 21-hydroxylase deficiency.

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Therapeutic implication

J Clin Endocrinol Metab 2026· JulRead

Parkinson's disease genetics across diverse ancestries: an observational genetic study of causal and risk variants with translational implications.

Parkinson's disease and monogenic parkinsonism

Recurrent variantTherapeutic implication

Lancet Neurol 2026· JulRead

To screen or not to screen G6PD deficiency in gNBS: insights from the BabyDetect pilot and current evidence.

G6PD deficiency and genomic newborn screening

Newborn screening

Eur J Hum Genet 2026· AugRead

Autosomal recessivePubMed

Genotype-refined 17OHP cut-offs diagnosing nonclassical CAH due to 21OH deficiency in children with premature pubarche.

Nonclassic congenital adrenal hyperplasia and premature pubarche

J Endocr Soc 2026· AugRead

Autosomal recessivePubMed

Beyond citrulline: The diagnostic accuracy of amino acid ratios in neonatal intrahepatic cholestasis caused by citrin deficiency.

Neonatal intrahepatic cholestasis caused by citrin deficiency

Newborn screeningTherapeutic implication

Mol Genet Metab 2026· JulRead

A Bayesian framework for longitudinal EHR and genetic discovery.

Penetrance of monogenic predisposition — disease trajectories and polygenic risk

Nature 2026· JulRead

Autosomal dominantPubMed

Arrhythmic Risk in Carriers of Predicted Deleterious Rare Variants in Dilated and Arrhythmogenic Cardiomyopathy Genes.

Dilated and arrhythmogenic cardiomyopathy in the general population

JACC Adv 2026· JulRead

Autosomal recessivePubMed

Defining Haplosufficiency in Autosomal Recessive Limb-Girdle Muscular Dystrophy Using Molecular Markers in Disease Carriers.

Autosomal recessive limb-girdle muscular dystrophies

Therapeutic implication

Neurol Genet 2026· JulRead

Impact of Cardiomyopathy and Arrhythmia Genetic Testing on Clinical Management Decisions

Inherited cardiomyopathies and arrhythmias

medRxiv 2026· JulRead

Chromosomal microarray analysis in 1292 fetuses with ultrasound soft markers during mid-term pregnancy.

Ultrasound soft markers in mid-trimester pregnancy

PrenatalPrenatal application

J Matern Fetal Neonatal Med 2026· JulRead

Autosomal recessivemedRxiv

Biallelic protein truncating EXOSC6 variants cause a neurodevelopmental disorder with cerebellar atrophy, ataxia, and global developmental delay

Neurodevelopmental disorder with ataxia and cerebellar atrophy (exosomopathy)

NeurodevelopmentNew geneFunctional SNV

medRxiv 2026· AugRead

Autosomal recessivePubMed

A deep intronic CPS1 variant causing pseudo-exon activation identified in an adult with molecularly unconfirmed urea cycle disorder.

Carbamoyl phosphate synthetase 1 deficiency, a urea cycle disorder

Metabolism / EpilepsyDeep intronic variantFunctional SNV

Biochem Biophys Res Commun 2026· JulRead

Autosomal dominantPubMed

Novel and Known DHX37 Variants in 46,XY DSD: Expanding the Genotypic and Phenotypic Spectrum.

46,XY differences of sex development

Phenotypic expansion

Genes (Basel) 2026· JulRead

Autosomal recessivePubMed

PALM3 and hearing loss: a potential dual diagnosis interfering with novel gene discovery.

Autosomal recessive non-syndromic hearing loss

Eur J Hum Genet 2026· JulRead

Autosomal recessivePubMed

Identification of a Duplication in the RP17 Locus in an Individual With Pathogenic CEP290 Variants: Implications for RP17 Variant Classification.

Invest Ophthalmol Vis Sci 2026· AugRead

References and sources

ARID1B — ARID1B-related neurodevelopmental disorders. Eur J Hum Genet 2026. PMID 42527582. Score 9/10. https://pubmed.ncbi.nlm.nih.gov/42527582/
G6PD — G6PD deficiency and genomic newborn screening. Eur J Hum Genet 2026. PMID 42538390. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42538390/
CYP21A2 — Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Endocrinol Metab 2026. PMID 42517590. Score 8/10. https://pubmed.ncbi.nlm.nih.gov/42517590/
GBA1 — Parkinson's disease and monogenic parkinsonism. Lancet Neurol 2026. PMID 42456684. Score 8/10. https://pubmed.ncbi.nlm.nih.gov/42456684/
CPS1 — Carbamoyl phosphate synthetase 1 deficiency, a urea cycle disorder. Biochem Biophys Res Commun 2026. PMID 42485798. Score 5/10. https://pubmed.ncbi.nlm.nih.gov/42485798/
DHX37 — 46,XY differences of sex development. Genes (Basel) 2026. PMID 42510869. Score 5/10. https://pubmed.ncbi.nlm.nih.gov/42510869/
Dilated and arrhythmogenic cardiomyopathy in the general population. JACC Adv 2026. PMID 42520655. Score 6/10. https://pubmed.ncbi.nlm.nih.gov/42520655/
PALM3 — Autosomal recessive non-syndromic hearing loss. Eur J Hum Genet 2026. PMID 42527583. Score 5/10. https://pubmed.ncbi.nlm.nih.gov/42527583/
CYP21A2 — Nonclassic congenital adrenal hyperplasia and premature pubarche. J Endocr Soc 2026. PMID 42540306. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42540306/
SLC25A13 — Neonatal intrahepatic cholestasis caused by citrin deficiency. Mol Genet Metab 2026. PMID 42430813. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42430813/
CAPN3 — Autosomal recessive limb-girdle muscular dystrophies. Neurol Genet 2026. PMID 42453854. Score 6/10. https://pubmed.ncbi.nlm.nih.gov/42453854/
Inherited cardiomyopathies and arrhythmias. medRxiv 2026. doi:10.64898/2026.07.22.26358740. Score 6/10. https://www.medrxiv.org/content/10.64898/2026.07.22.26358740v1
Ultrasound soft markers in mid-trimester pregnancy. J Matern Fetal Neonatal Med 2026. PMID 42528336. Score 6/10. https://pubmed.ncbi.nlm.nih.gov/42528336/
CEP290 — Cone dystrophy. Invest Ophthalmol Vis Sci 2026. PMID 42545071. Score 5/10. https://pubmed.ncbi.nlm.nih.gov/42545071/
EXOSC6 — Neurodevelopmental disorder with ataxia and cerebellar atrophy (exosomopathy). medRxiv 2026. doi:10.64898/2026.07.30.26359120. Score 6/10. https://www.medrxiv.org/content/10.64898/2026.07.30.26359120v1
Penetrance of monogenic predisposition — disease trajectories and polygenic risk. Nature 2026. PMID 42457967. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42457967/