Constitutional genetics

Week of 10 November 2026

15 articles

Geno'X Veille — genox-veille.fr

Key takeaways this week

►LIFR — Stüve-Wiedemann syndrome becomes a multisystem disorder of surviving children: 22 individuals, neurodevelopmental disorders, allergy and hyperinflammatory courses.
►HCN1 — 43 variants sorted into four functional classes: the direction of channel dysfunction predicts epilepsy and its severity in 50 patients.
►COL4A3 / COL4A4 — dominant Alport prevalence falls to one in 283: in silico curation inflates the control rate by 91% and the PM2 criterion needs revision.
►SCN2A — 48% of patients have a genotype compatible with an already developed antisense therapy, selected through diagnostic genome sequencing.
►BECN1 — candidate biallelic variants in a recessive neurodevelopmental disorder, with mouse and zebrafish models and AMPA receptor dysregulation (preprint).

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HCN1

PubMed

Comprehensive classification of HCN1 variants linked to neurodevelopmental disorders with and without epilepsy

Neurodevelopmental disorders with or without epilepsy, including developmental and epileptic encephalopathies

NeurodevelopmentFunctional SNV

Proc Natl Acad Sci U S A 2026· NovRead

LIFR

Autosomal recessivePubMed

Hypomorphic biallelic LIFR variants define a multisystem disorder with survival beyond infancy and hyperinflammatory vulnerability

Stüve-Wiedemann syndrome (LIFR deficiency) with survival beyond infancy

NeurodevelopmentPhenotypic expansionFunctional SNV

Front Immunol 2026· OctRead

COL4A3, COL4A4

Autosomal dominantPubMed

Systematic overestimation using in silico-driven curation in a population database caused reevaluation of the genetic prevalence of Alport Syndrome

Autosomal dominant Alport syndrome

Kidney Int 2026· NovRead

FGFR3

PubMed

Vosoritide therapy in Brazil: Consensus on the Diagnosis, Monitoring, and Management of Achondroplasia

Achondroplasia treated with vosoritide

Therapeutic implication

Orphanet J Rare Dis 2026· AugRead

WGS / Diagnosis

PubMed

Optimizing Genetic Analyses for Movement Disorders: A Unified Panel Approach and Targeted Reanalysis of 4,046 Clinical Exomes

Genetic movement disorders

WGS / Diagnosis

Mov Disord 2026· NovRead

Newborn screening

PubMed

Clinical utility and implementation of genomic newborn screening: findings from the SNUseq Baby Project

Genomic newborn screening for early-onset, treatable conditions

Newborn screening

Eur J Hum Genet 2026· NovRead

TERT

Autosomal dominantPubMed

Genomic ascertainment refines the population prevalence and phenotype associations of germline TERT variants

Telomere biology disorders: pulmonary fibrosis, liver disease, bone marrow failure, head and neck squamous cell carcinoma

PLoS Genet 2026· NovRead

GBA1

PubMed

Understanding the Pattern of Cognitive Decline in GBA1-Related Parkinson's Disease: An Exploratory Longitudinal Multi-Cohort Study

Parkinson's disease in carriers of a pathogenic GBA1 variant

Ann Neurol 2026· NovRead

ABCD1

X-linkedPubMed

Evaluating the feasibility and diagnostic performance of a multi-tier newborn screening algorithm for X-linked adrenoleukodystrophy in Denmark

X-linked adrenoleukodystrophy

Newborn screening

Mol Genet Metab 2026· OctRead

WGS / Diagnosis

PubMed

Upfront whole genome and transcriptome sequencing to improve diagnosis in inherited bone marrow failure syndromes

Inherited bone marrow failure syndromes

WGS / Diagnosis

Blood 2026· NovRead

JKAMP

Autosomal recessivePubMed

Biallelic variants in the ERAD pathway gene JKAMP cause a neurodevelopmental disorder with urogenital manifestations

Syndromic neurodevelopmental disorder with urogenital manifestations, ERAD pathway-related

NeurodevelopmentRecurrent variant

Genet Med 2026· NovRead

SCN2A

Autosomal dominantPubMed

⭐ Featured

Scaling haplospecific antisense oligonucleotides from N-of-1 to broad use in genetic disease populations by diplotyping

SCN2A-complex neurodevelopmental disorder, with gain of function or mixed dysfunction

NeurodevelopmentTherapeutic implication

Am J Hum Genet 2026· NovRead

Prenatal

PubMed

Prenatal Trio Exome Sequencing in Low-Risk Pregnancies: Diagnostic Yield and Clinical Implications

Structurally normal pregnancies investigated by trio exome sequencing

PrenatalPrenatal application

Clin Genet 2026· NovRead

Neurodevelopment

PubMed

Molecular Diagnosis in Children With Febrile Seizures: Beyond the Conventional Clinical Classification

Simple and complex febrile seizures in children

Neurodevelopment

Ann Clin Transl Neurol 2026· NovRead

BECN1

Autosomal recessivePubMed

Biallelic BECN1 variants cause neurodevelopmental disorders via AMPA receptor dysregulation

Neurodevelopmental disorder with impaired social interaction

NeurodevelopmentNew geneNew mechanism

medRxiv 2026· OctRead

References and sources

HCN1 — Neurodevelopmental disorders with or without epilepsy, including developmental and epileptic encephalopathies. Proc Natl Acad Sci U S A 2026. PMID 42981027. Score 8/10. https://pubmed.ncbi.nlm.nih.gov/42981027/
LIFR — Stüve-Wiedemann syndrome (LIFR deficiency) with survival beyond infancy. Front Immunol 2026. PMID 42973632. Score 8/10. https://pubmed.ncbi.nlm.nih.gov/42973632/
COL4A3, COL4A4 — Autosomal dominant Alport syndrome. Kidney Int 2026. PMID 42988165. Score 8/10. https://pubmed.ncbi.nlm.nih.gov/42988165/
FGFR3 — Achondroplasia treated with vosoritide. Orphanet J Rare Dis 2026. PMID 42983735. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42983735/
Genetic movement disorders. Mov Disord 2026. PMID 42973290. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42973290/
Genomic newborn screening for early-onset, treatable conditions. Eur J Hum Genet 2026. PMID 42988931. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42988931/
TERT — Telomere biology disorders: pulmonary fibrosis, liver disease, bone marrow failure, head and neck squamous cell carcinoma. PLoS Genet 2026. PMID 42986891. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42986891/
GBA1 — Parkinson's disease in carriers of a pathogenic GBA1 variant. Ann Neurol 2026. PMID 42969188. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42969188/
ABCD1 — X-linked adrenoleukodystrophy. Mol Genet Metab 2026. PMID 42987733. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42987733/
Inherited bone marrow failure syndromes. Blood 2026. PMID 42986897. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42986897/
JKAMP — Syndromic neurodevelopmental disorder with urogenital manifestations, ERAD pathway-related. Genet Med 2026. PMID 42992451. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42992451/
SCN2A — SCN2A-complex neurodevelopmental disorder, with gain of function or mixed dysfunction. Am J Hum Genet 2026. PMID 42987799. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42987799/
Structurally normal pregnancies investigated by trio exome sequencing. Clin Genet 2026. PMID 42994812. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42994812/
Simple and complex febrile seizures in children. Ann Clin Transl Neurol 2026. PMID 42995169. Score 6/10. https://pubmed.ncbi.nlm.nih.gov/42995169/
BECN1 — Neurodevelopmental disorder with impaired social interaction. medRxiv 2026. PMID 42999402. Score 6/10. https://pubmed.ncbi.nlm.nih.gov/42999402/

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3 November 2026