Elucidating the Role of SET as a Key Contributor to Neurodevelopmental Disability Within the 9q34.11 Deletion Syndrome Interval.

Systematic genotype-phenotype mapping and transcriptomic analyses highlight SEMA6A as a candidate for neuronal migration defects in 5q22-q23 deletions.

THUMPD1-Related Neurodevelopmental Disorder: A Novel Homozygous Loss-of-Function Variant with an Unusual Skeletal Phenotype - A Case Report.

The presence of the finding in only 1 of the 2 affected siblings, both of whom carry the same homozygous variant, limits the strength of the genotype-phenotype association, and a definitive causal relationship between the THUMPD1 variant and the skeletal phenotype cannot be established.

Delineation of a Novel Mirror Syndrome: NFIC Variants Cause Syndromic Intellectual Disability With Macrocephaly.

Nuclear factor I (NFI) transcription factors regulate neural stem and progenitor differentiation during brain development. While NFIA, NFIB, and NFIX are linked to neurodevelopmental disorders, the role of NFIC (MIM: 600729) in human disease remains unclear. This study aimed to determine whether NFIC contributes to a neurodevelopmental syndrome, define its phenotype, and assess dosage-dependent effects. We established the first cohort of 11 individuals, including NFIC deletions and single nucleotide variants. Genotype-phenotype correlations, including critical region mapping, were performed. Murine data and bioinformatics were integrated to explore underlying pathomechanisms. We report 11 individuals with NFIC variants, including four with de novo SNVs and seven with deletions encompassing the gene, of whom nine have not been previously reported. A core phenotype of syndromic intellectual disability and macrocephaly was delineated. Opposing cranial phenotypes relative to proximal 19p13.3 duplication cases support a dosage-sensitive effect and a mirror-syndrome model. NFIC-related disorder represents a novel neurodevelopmental syndrome characterized by intellectual disability and macrocephaly, highlighting the importance of NFIC dosage supporting a mirror-syndrome model.

A novel mutation in SETD1A is associated with early-onset epilepsy—a rare case report

This study may expand the mutation and phenotypic spectrum of SETD1A-related disorders, establishing the relationship between SETD1A variants and isolated early-onset epilepsy without accompanying severe neurodevelopmental deficits, and highlighting the value of genetic testing in infants with unexplained epilepsy.

Clinical Phenotypes Associated with NRXN1 Deletions in Five Children with Autism Spectrum Disorder in Oman

Clinical heterogeneity among children with NRXN1 deletions illustrates clinical heterogeneity among children with autism spectrum disorder and supports the need for larger studies to better define genotype-phenotype relationships.

Biallelic EZH1 Nonsense Novel Variant in Two Siblings with Neurodevelopmental Disorder and Central Precocious Puberty: A Case Report from a Consanguineous Saudi Family

This study expands the clinical, genetic, and molecular spectrum of EZH1-associated neurodevelopmental disorders by demonstrating that reduced EZH1 expression is consistent with a loss-of-function disease mechanism.