Constitutional genetics

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Constitutional genetics

Week of 30 June 2026

19 articles

Geno'X Veille — genox-veille.fr

Key takeaways this week

►EIF1AX — novel X-linked syndromic neurodevelopmental gene, validated by Drosophila model.
►GIT1 — novel recognizable recessive neurodevelopmental disorder, validated in fibroblasts and zebrafish.
►KCNJ4 — novel epileptic channelopathy with dual gain/loss-of-function mechanism.
►WES-negative — long-read ICLR and OGM as second-tier testing resolve unexplained neurodevelopmental disorders.
►Long-read — in a well pre-screened cohort, the additional diagnostic yield is only 1%.

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Hemizygous loss-of-function variants of EIF1AX are associated with a syndromic neurodevelopmental disorder

X-linked syndromic neurodevelopmental disorder

NeurodevelopmentNew geneFunctional SNV

Eur J Hum Genet 2026· JunRead

WGS / Diagnosis

Autosomal recessivePubMed

Systematic analysis of homozygous autosomal copy number losses in exomes improves diagnostic yield and uncovers ultra-rare recessive disorders

Ultra-rare recessive disorders — homozygous copy number losses on exome

WGS / DiagnosisNew gene

Eur J Hum Genet 2026· JunRead

Diagnostic Yield and Clinical Impact of Comprehensive WES/WGS Testing Beyond Common Genetic Causes in Hereditary Optic Atrophy

Hereditary optic atrophy

WGS / Diagnosis

Clin Genet 2026· JunRead

WGS / Diagnosis

Autosomal dominantPubMed

Integrative genetic and functional analysis of autosomal dominant hearing loss in 108 multigenerational families

Autosomal dominant hearing loss

WGS / DiagnosisDeep intronic variantFunctional SNV

J Mol Med (Berl) 2026· JunRead

Autosomal dominantPubMed

KCNJ4 variants disrupt inward-rectifier potassium channel function and cause refractory epilepsy

Refractory epilepsy / developmental and epileptic encephalopathy

NeurodevelopmentNew geneFunctional SNV

Epilepsia 2026· MarRead

Autosomal recessivePubMed

A lethal form of ASCC3 disease: severe global developmental delay, axial hypotonia, hypoplasia of corpus callosum, hypothyroidism and micropenis

Lethal form of *ASCC3*-related disease

NeurodevelopmentPhenotypic expansion

HGG Adv 2026· JunRead

Autosomal recessivePubMed

GIT1 loss of function causes a recognizable syndromic neurodevelopmental disorder

Recognizable syndromic neurodevelopmental disorder

NeurodevelopmentNew geneFunctional SNV

Brain 2026· JunRead

Structural Variation Sequencing of 26 Amniotic Fluid Samples With Partial Gene Duplications and Postnatal Follow-Up of the Fetuses

Prenatal diagnosis of partial gene duplications

PrenatalPrenatal application

Prenat Diagn 2026· JunRead

Identifying genetic causes and establishing a diagnostic approach for WES-negative pediatric population with neurodevelopmental disorder

WES-negative pediatric neurodevelopmental disorder

Long-read WGSLong-read sequencing

Eur J Hum Genet 2026· JunRead

Expanded carrier screening — East Asian-specific variants

Autosomal recessivePubMed

Expanded carrier screening in a Southwestern Chinese population indicates East Asian specific low-frequency pathogenic variants account for nearly half of the at-risk couple rate

Expanded carrier screening — East Asian-specific variants

Recurrent variant

J Med Genet 2026· JunRead

Autosomal dominantPubMed

Identification of a novel pathogenic variant in MYLK in an Iranian family with non-syndromic familial aortic aneurysm and dissection by whole-exome sequencing and literature review

Non-syndromic familial thoracic aortic aneurysm and dissection

CardiologyRecurrent variant

BMC Med Genomics 2026· JunRead

Autosomal recessivePubMed

Identification of biallelic loss-of-function PREP variants in three individuals with syndromic intellectual disability

Syndromic intellectual disability

NeurodevelopmentFunctional SNV

J Med Genet 2026· JunRead

Autosomal dominantPubMed

Integrative analysis of drug-gene signatures in human pluripotent stem cells reveals prazosin as a novel SQSTM1 regulator for ALS therapeutics

FTD/ALS type 3 from *SQSTM1* haploinsufficiency

Therapeutic implication

Stem Cell Reports 2026· JunRead

Chromosomal Microarray Analysis in Critically Ill Neonates and Children: Diagnostic Yield and Clinical Utility

Chromosomal abnormalities in neonatal and pediatric intensive care

Life (Basel) 2026· JunRead

Refining the diagnosis of 46,XY disorders of sex development: insight from whole-exome sequencing

46,XY disorders of sex development

Orphanet J Rare Dis 2026· JunRead

Functional characterisation and pathological significance of variants of MEF2C promoter in tetralogy of Fallot

Tetralogy of Fallot

CardiologyFunctional SNV

J Med Genet 2026· JunRead

Autosomal dominantPubMed

Genetic spectrum and clinical features of PMP22 point mutations in Japanese Charcot-Marie-Tooth disease

Charcot-Marie-Tooth disease / *PMP22*-related neuropathies

NeurologyPhenotypic expansion

J Neurol 2026· JunRead

Structural variant discovery and diagnostic impact in rare diseases from short-read and long-read sequencing

Rare diseases — structural variants from short-read vs long-read sequencing

Long-read WGSLong-read sequencing

medRxiv 2026· JunRead

Autosomal recessivePubMed

Clinical and genetic characteristics of RPE65-associated inherited retinal degeneration in Koreans

*RPE65*-associated inherited retinal degeneration

Newborn screeningTherapeutic implication

Sci Rep 2026· JunRead

References and sources

EIF1AX — X-linked syndromic neurodevelopmental disorder. Eur J Hum Genet 2026. PMID 42337333. Score 10/10. https://pubmed.ncbi.nlm.nih.gov/42337333/
Ultra-rare recessive disorders — homozygous copy number losses on exome. Eur J Hum Genet 2026. PMID 42362802. Score 10/10. https://pubmed.ncbi.nlm.nih.gov/42362802/
OPA1 — Hereditary optic atrophy. Clin Genet 2026. PMID 42363686. Score 10/10. https://pubmed.ncbi.nlm.nih.gov/42363686/
Autosomal dominant hearing loss. J Mol Med (Berl) 2026. PMID 42371110. Score 10/10. https://pubmed.ncbi.nlm.nih.gov/42371110/
KCNJ4 — Refractory epilepsy / developmental and epileptic encephalopathy. Epilepsia 2026. PMID 41830586. Score 9/10. https://onlinelibrary.wiley.com/doi/10.1002/epi.70153?af=R
ASCC3 — Lethal form of *ASCC3*-related disease. HGG Adv 2026. PMID 42337909. Score 9/10. https://pubmed.ncbi.nlm.nih.gov/42337909/
GIT1 — Recognizable syndromic neurodevelopmental disorder. Brain 2026. PMID 42360756. Score 9/10. https://pubmed.ncbi.nlm.nih.gov/42360756/
Prenatal diagnosis of partial gene duplications. Prenat Diagn 2026. PMID 42371673. Score 9/10. https://pubmed.ncbi.nlm.nih.gov/42371673/
WES-negative pediatric neurodevelopmental disorder. Eur J Hum Genet 2026. PMID 42337331. Score 8/10. https://pubmed.ncbi.nlm.nih.gov/42337331/
Expanded carrier screening — East Asian-specific variants. J Med Genet 2026. PMID 41932824. Score 8/10. https://pubmed.ncbi.nlm.nih.gov/41932824/
MYLK — Non-syndromic familial thoracic aortic aneurysm and dissection. BMC Med Genomics 2026. PMID 42365314. Score 8/10. https://pubmed.ncbi.nlm.nih.gov/42365314/
PREP — Syndromic intellectual disability. J Med Genet 2026. PMID 42362369. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42362369/
SQSTM1 — FTD/ALS type 3 from *SQSTM1* haploinsufficiency. Stem Cell Reports 2026. PMID 42349423. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42349423/
Chromosomal abnormalities in neonatal and pediatric intensive care. Life (Basel) 2026. PMID 42355559. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42355559/
AR — 46,XY disorders of sex development. Orphanet J Rare Dis 2026. PMID 42365275. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42365275/
MEF2C — Tetralogy of Fallot. J Med Genet 2026. PMID 42373308. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42373308/
PMP22 — Charcot-Marie-Tooth disease / *PMP22*-related neuropathies. J Neurol 2026. PMID 42371158. Score 7/10. https://pubmed.ncbi.nlm.nih.gov/42371158/
RPE65 — *RPE65*-associated inherited retinal degeneration. Sci Rep 2026. PMID 42365082. Score 6/10. https://pubmed.ncbi.nlm.nih.gov/42365082/
Rare diseases — structural variants from short-read vs long-read sequencing. medRxiv 2026. doi:10.64898/2026.06.22.26356238. Score 7/10. https://www.medrxiv.org/content/10.64898/2026.06.22.26356238v1