Constitutional genetics

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Constitutional genetics

Week of 21 July 2026

19 articles

Geno'X Veille — genox-veille.fr

Key takeaways this week

►KATNA1 — a new gene for dominant macular dystrophy, possibly ~4 % of unexplained cases.
►Combined SMA + SCID newborn screening: four infants treated presymptomatically out of 32,289 newborns.
►MYBPC3 — large-scale functional mapping to reclassify VUS in hypertrophic cardiomyopathy.
►TBX1 — functional noncoding enhancer variants contribute to tetralogy of Fallot.
►long-read — targeted capture and nanopore uncover SVs and intronic variants in recessive disorders.

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Autosomal dominantPubMed

Missense variants in KATNA1 alter microtubule dynamics and underlie dominant macular dystrophy.

Dominant macular dystrophy (inherited retinal disease)

New geneFunctional SNV

Res Sq 2026· JulRead

Newborn screening

Five-year experience of a combined newborn screening for spinal muscular atrophy and severe combined immunodeficiency in Liguria, Italy.

Spinal muscular atrophy (SMA) and severe combined immunodeficiency (SCID)

Newborn screeningTherapeutic implication

Eur J Hum Genet 2026· JulRead

Autosomal dominantPubMed

Scaled Multidimensional Assays of Variant Effect Identify Sequence-Function Relationships in Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM)

CardiologyFunctional SNVVUS reclassified

Circulation 2026· JulRead

Functional noncoding variants within the TBX1 enhancer contribute to tetralogy of Fallot.

Tetralogy of Fallot (congenital heart disease)

WGS / DiagnosisNew mechanismFunctional SNV

Sci China Life Sci 2026· JulRead

Autosomal recessivePubMed

Strømme syndrome: the clinical and molecular spectrum associated with variants in CENPF.

Strømme syndrome (syndromic microcephaly)

Phenotypic expansion

Eur J Hum Genet 2026· JulRead

Autosomal dominantPubMed

Expanding the Clinical and Molecular Spectrum of TUBB2B Through Distinct Variants Identified Across Multiple Families.

Tubulinopathy (neurodevelopmental disorder)

NeurodevelopmentPhenotypic expansion

HGG Adv 2026· JulRead

WGS / Diagnosis

Unveiling ocular developmental disorders through short-read whole-genome sequencing.

Congenital eye malformations

WGS / Diagnosis

Eur J Hum Genet 2026· JulRead

Autosomal recessivePubMed

Unraveling missing variants through target capture-based long-read sequencing in autosomal recessive disorders.

Autosomal recessive disorders (missing variants)

Long-read WGSLong-read sequencingDeep intronic variant

Eur J Hum Genet 2026· JulRead

Diagnostic discovery of structural variants causing foveal hypoplasia using SVRare and long-read nanopore sequencing.

Foveal hypoplasia / ocular albinism (structural variants)

Long-read WGSLong-read sequencing

Eur J Hum Genet 2026· JulRead

Autosomal dominantPubMed

Clinical and molecular characterization of TCF12 variants in an Asian pediatric cohort with craniosynostosis.

Coronal craniosynostosis

Recurrent variant

BMC Med Genomics 2026· JulRead

Autosomal dominantPubMed

Clinical and genetic spectrum of RHOBTB2-related disorders: A study integrating Chinese and international cohorts for genotype-phenotype correlations and clinical subtyping.

RHOBTB2-related developmental and epileptic encephalopathy

NeurodevelopmentRecurrent variantPhenotypic expansion

Epilepsia 2026· JulRead

Autosomal recessivePubMed

A Multi-Center Integrative Cohort Characterizing the Genetic, Clinical, and Transcriptomic Features of ACP5 Deficiency.

Spondyloenchondrodysplasia with immune dysregulation (SPENCDI)

Recurrent variantTherapeutic implication

Arthritis Rheumatol 2026· JulRead

Autosomal recessivePubMed

MORF4L1, encoding a chromatin remodeler, is mutated in a recognizable dysmorphic neurodevelopmental disorder.

Dysmorphic neurodevelopmental disorder

NeurodevelopmentNew geneFunctional SNV

Sci Rep 2026· JulRead

Autosomal recessivePubMed

Biallelic TXNIP deficiency is associated with a multisystemic metabolic disease.

TXNIP-related multisystemic metabolic disease

CardiologyPhenotypic expansionFunctional SNV

Mol Metab 2026· JulRead

Autosomal dominantPubMed

Expanding the phenotypic and genotypic spectrum of KCNT1-related epilepsies.

KCNT1-related epilepsies

Metabolism / EpilepsyPhenotypic expansionRecurrent variant

Brain Commun 2026· JulRead

Autosomal dominantPubMed

NKX2-1 Downstream Regulatory Structural Variants Explain a Substantial Proportion of Molecular Diagnoses in Patients With Benign Hereditary Chorea.

Benign hereditary chorea (NKX2-1-related disorders)

NeurologyNew mechanism

Mov Disord 2026· JulRead

WGS / Diagnosis

Dissecting the functional landscape of rare diseases through genomic variation in a heterogeneous cohort of 11,000 patients.

Rare diseases — guided reanalysis of unsolved cases

WGS / Diagnosis

medRxiv 2026· JulRead

Autosomal dominantPubMed

SHOC2 Is a Novel Cause of Central Conducting Lymphatic Anomaly.

Central conducting lymphatic anomaly (RASopathy)

Phenotypic expansionFunctional SNV

Am J Med Genet A 2026· JulRead

Autosomal recessivePubMed

Novel SLC10A2 variants induce primary bile acid malabsorption and dysbiosis with IBD-like features.

Primary bile acid malabsorption (IBD phenocopy)

Recurrent variantTherapeutic implication

Inflamm Bowel Dis 2026· JulRead

References and sources

KATNA1 — Dominant macular dystrophy (inherited retinal disease). Res Sq 2026. PMID 42466416. Score 9/10. https://pubmed.ncbi.nlm.nih.gov/42466416/
Spinal muscular atrophy (SMA) and severe combined immunodeficiency (SCID). Eur J Hum Genet 2026. PMID 42471517. Score 8/10. https://pubmed.ncbi.nlm.nih.gov/42471517/
MYBPC3 — Hypertrophic cardiomyopathy (HCM). Circulation 2026. PMID 42437345. Score 8/10. https://pubmed.ncbi.nlm.nih.gov/42437345/
TBX1 — Tetralogy of Fallot (congenital heart disease). Sci China Life Sci 2026. PMID 42446827. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42446827/
CENPF — Strømme syndrome (syndromic microcephaly). Eur J Hum Genet 2026. PMID 42471516. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42471516/
TUBB2B — Tubulinopathy (neurodevelopmental disorder). HGG Adv 2026. PMID 42470103. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42470103/
Congenital eye malformations. Eur J Hum Genet 2026. PMID 42448966. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42448966/
Autosomal recessive disorders (missing variants). Eur J Hum Genet 2026. PMID 42477409. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42477409/
Foveal hypoplasia / ocular albinism (structural variants). Eur J Hum Genet 2026. PMID 42477408. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42477408/
TCF12 — Coronal craniosynostosis. BMC Med Genomics 2026. PMID 42443919. Score 6/10. https://pubmed.ncbi.nlm.nih.gov/42443919/
RHOBTB2 — RHOBTB2-related developmental and epileptic encephalopathy. Epilepsia 2026. PMID 42470352. Score 6/10. https://onlinelibrary.wiley.com/doi/10.1002/epi.70286?af=R
ACP5 — Spondyloenchondrodysplasia with immune dysregulation (SPENCDI). Arthritis Rheumatol 2026. PMID 42459138. Score 6/10. https://pubmed.ncbi.nlm.nih.gov/42459138/
MORF4L1 — Dysmorphic neurodevelopmental disorder. Sci Rep 2026. PMID 42457791. Score 6/10. https://pubmed.ncbi.nlm.nih.gov/42457791/
TXNIP — TXNIP-related multisystemic metabolic disease. Mol Metab 2026. PMID 42448226. Score 6/10. https://pubmed.ncbi.nlm.nih.gov/42448226/
KCNT1 — KCNT1-related epilepsies. Brain Commun 2026. PMID 42453761. Score 6/10. https://pubmed.ncbi.nlm.nih.gov/42453761/
NKX2-1 — Benign hereditary chorea (NKX2-1-related disorders). Mov Disord 2026. PMID 42464514. Score 6/10. https://pubmed.ncbi.nlm.nih.gov/42464514/
Rare diseases — guided reanalysis of unsolved cases. medRxiv 2026. doi:10.64898/2026.06.10.26355349. Score 6/10. https://www.medrxiv.org/content/10.64898/2026.06.10.26355349v2
SHOC2 — Central conducting lymphatic anomaly (RASopathy). Am J Med Genet A 2026. PMID 42454412. Score 5/10. https://pubmed.ncbi.nlm.nih.gov/42454412/
SLC10A2 — Primary bile acid malabsorption (IBD phenocopy). Inflamm Bowel Dis 2026. PMID 42435330. Score 5/10. https://pubmed.ncbi.nlm.nih.gov/42435330/