Constitutional genetics

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Constitutional genetics

Week of 3 June 2026

16 articles

Geno'X Veille — genox-veille.fr

Key takeaways this week

►BORCS5 — new lysosomal gene, NDD-to-lethal arthrogryposis spectrum, zebrafish model.
►PHEX — burosumab effective and safe from the first months of life in XLH.
►FGF14 — GAA expansion underdiagnosed in 13% of unsolved sporadic ataxias.
►PRKN — alternative translation initiation mechanism explaining delayed onset of exon 2 deletion.

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Autosomal recessivePubMed

Pathogenic variants in BORCS5 cause a spectrum of neurodevelopmental and neurodegenerative disorders with lysosomal dysfunction.

Neurodevelopmental and neurodegenerative spectrum with lysosomal dysfunction

NeurodevelopmentNew geneNew mechanism

J Clin Invest 2026· JunRead

Safety, tolerability, pharmacokinetics, and efficacy of burosumab in infants with X-linked hypophosphataemia: an open-label, multicentre, non-randomised study.

X-linked hypophosphataemia (XLH) — infants

Therapeutic implication

Lancet Diabetes Endocrinol 2026· JunRead

Gene burden meta-analysis of 748 879 individuals identifies LGI1-ADAM23 protein complex association with epilepsy.

Epilepsy — gene burden meta-analysis, LGI1-ADAM23 protein complex

Metabolism / EpilepsyNew gene

Epilepsia 2026· MayRead

WGS / Diagnosis

Fibroblast Transcriptomics in Molecular Diagnostics of a Comprehensive Dystonia Cohort.

Dystonia — molecular diagnostics by fibroblast transcriptomics

WGS / DiagnosisFunctional SNV

Ann Neurol 2026· JunRead

Autosomal dominantPubMed

Multimodal Genotype-Phenotype Analysis in SMARCB1-Associated Developmental Disorders.

Coffin-Siris syndrome and SMARCB1-associated developmental disorders

NeurodevelopmentPhenotypic expansion

Genet Med 2026· MayRead

Autosomal recessivePubMed

Alternative Translation Initiation in PRKN Delays the Onset of Parkinson's Disease and Offers a Therapeutic Target.

PRKN autosomal recessive Parkinson's disease

New mechanismFunctional SNV

Ann Neurol 2026· MayRead

Autosomal dominantPubMed

High Prevalence of SOD1 Pathogenic Variants in the UK Biobank: Implications for Early Intervention in Amyotrophic Lateral Sclerosis.

SOD1-ALS — biobank prevalence and implications for preemptive screening

Therapeutic implication

Ann Neurol 2026· JunRead

Autosomal dominantPubMed

The Age at Onset of LRRK2 p.Gly2019Ser Parkinson's Disease Across Ancestries and Countries of Origin.

LRRK2 p.Gly2019Ser Parkinson's disease — age at onset by ancestry

Recurrent variant

Ann Neurol 2026· MayRead

Autosomal dominantPubMed

GAA-FGF14 Ataxia Is a Frequently Overlooked Cause of Sporadic Adult-Onset Ataxia.

GAA-FGF14 ataxia (SCA27B) — adult-onset autosomal dominant cerebellar ataxia

Long-read WGSRepeat expansionLong-read sequencing

Clin Genet 2026· MayRead

Genotype-Phenotype Spectrum of Non-Syndromic Monogenic Obesity in a National Paediatric Cohort.

Non-syndromic monogenic obesity — leptin-melanocortin pathway

WGS / DiagnosisRecurrent variant

Pediatr Obes 2026· JunRead

Rapid Genome and Exome Sequencing in Inpatients: Clinical Impact at a Tertiary Academic Medical Center.

Rapid genome/exome sequencing in inpatients — clinical impact

Rapid WGSClinical pipeline

Am J Med Genet A 2026· JunRead

Novel Haplotype-Based Noninvasive Prenatal Diagnosis for Recessive Single-Gene Disorders: A Proof-of-Concept Study.

Noninvasive prenatal diagnosis — recessive single-gene disorders

Long-read WGSPrenatal applicationLong-read sequencing

Clin Genet 2026· JunRead

WGS / Diagnosis

Identification of monogenic variants in steroid-resistant and steroid-sensitive nephrotic syndrome.

Steroid-resistant nephrotic syndrome (SRNS) — molecular diagnosis by exome sequencing

WGS / Diagnosis

Pediatr Nephrol 2026· JunRead

WGS / Diagnosis

A Proposed Clinical Diagnostic Framework for Short Telomere Syndrome.

Short Telomere Syndrome

WGS / DiagnosisNew recommendation

Clin Genet 2026· MayRead

Impact of Rapid Exome Sequencing on Pediatric Patients With Cardiomyopathy and Acute Heart Failure.

Pediatric cardiomyopathy with acute heart failure — rapid exome sequencing

Rapid WESTherapeutic implication

Am J Med Genet A 2026· JunRead

Autosomal recessivePubMed

Gene therapy outcomes in young patients with RPE65-retinal degeneration.

RPE65-associated Leber congenital amaurosis (RPE65-LCA)

Therapeutic implication

Can J Ophthalmol 2026· JunRead

References and sources

BORCS5 — Neurodevelopmental and neurodegenerative spectrum with lysosomal dysfunction. J Clin Invest 2026. PMID 42012897. Score 9/10. https://pubmed.ncbi.nlm.nih.gov/42012897/
PHEX — X-linked hypophosphataemia (XLH) — infants. Lancet Diabetes Endocrinol 2026. PMID 42044650. Score 8/10. https://pubmed.ncbi.nlm.nih.gov/42044650/
SMARCB1 — Coffin-Siris syndrome and SMARCB1-associated developmental disorders. Genet Med 2026. PMID 42206491. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42206491/
Short Telomere Syndrome. Clin Genet 2026. PMID 42219160. Score 5/10. https://pubmed.ncbi.nlm.nih.gov/42219160/
FGF14 — GAA-FGF14 ataxia (SCA27B) — adult-onset autosomal dominant cerebellar ataxia. Clin Genet 2026. PMID 42204984. Score 6/10. https://pubmed.ncbi.nlm.nih.gov/42204984/
LGI1 — Epilepsy — gene burden meta-analysis, LGI1-ADAM23 protein complex. Epilepsia 2026. PMID 42216960. Score 8/10. https://pubmed.ncbi.nlm.nih.gov/42216960/
PRKN — PRKN autosomal recessive Parkinson's disease. Ann Neurol 2026. PMID 41724727. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/41724727/
LEPR — Non-syndromic monogenic obesity — leptin-melanocortin pathway. Pediatr Obes 2026. PMID 42210527. Score 6/10. https://pubmed.ncbi.nlm.nih.gov/42210527/
SOD1 — SOD1-ALS — biobank prevalence and implications for preemptive screening. Ann Neurol 2026. PMID 41852184. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/41852184/
Rapid genome/exome sequencing in inpatients — clinical impact. Am J Med Genet A 2026. PMID 41704091. Score 6/10. https://pubmed.ncbi.nlm.nih.gov/41704091/
Noninvasive prenatal diagnosis — recessive single-gene disorders. Clin Genet 2026. PMID 41681029. Score 6/10. https://pubmed.ncbi.nlm.nih.gov/41681029/
RPE65 — RPE65-associated Leber congenital amaurosis (RPE65-LCA). Can J Ophthalmol 2026. PMID 41679721. Score 4/10. https://pubmed.ncbi.nlm.nih.gov/41679721/
Dystonia — molecular diagnostics by fibroblast transcriptomics. Ann Neurol 2026. PMID 41623120. Score 8/10. https://pubmed.ncbi.nlm.nih.gov/41623120/
LRRK2 — LRRK2 p.Gly2019Ser Parkinson's disease — age at onset by ancestry. Ann Neurol 2026. PMID 41735653. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/41735653/
Steroid-resistant nephrotic syndrome (SRNS) — molecular diagnosis by exome sequencing. Pediatr Nephrol 2026. PMID 41575523. Score 6/10. https://pubmed.ncbi.nlm.nih.gov/41575523/
Pediatric cardiomyopathy with acute heart failure — rapid exome sequencing. Am J Med Genet A 2026. PMID 41572441. Score 5/10. https://pubmed.ncbi.nlm.nih.gov/41572441/