We describe six individuals from five unrelated families harboring variants in ATG12, a core autophagy gene, resulting in a neurodevelopmental disorder. Using patient tissue and in vitro and in vivo m...

We identify bi-allelic BLOC1S1 variants in 11 individuals with severe neurodevelopmental disease, including leukodystrophy, epilepsy, spasticity, and optic atrophy. Functional analyses demonstrate imp...

Bi-allelic loss-of-function variants in JKAMP cause a neurodevelopmental syndrome. A zebrafish jkamp knockout recapitulates key disease features. Functional studies show that JKAMP deficiency impairs ...

PGBD5 is required for brain development in humans and mice through genetic and nongenetic mechanisms.

Biallelic variants in CHKA, which encodes the first enzyme in the CDP-choline pathway for the synthesis of phosphatidylcholine, cause an inherited disorder characterized by epilepsy, microcephaly, and...

Background Primary brain calcifications are observed in several inherited diseases due to different pathogenic mechanisms, including the disruption of the neurovascular unit, mitochondrial dysfuncti...

Bi-allelic variants in RPS6KC1 cause a neurodevelopmental disorder with features overlapping with Coffin-Lowry syndrome. Functional studies reveal impaired ribosomal protein synthesis, disrupted lipid...

Objective Autophagy is a fundamental biological pathway with vital roles in intracellular homeostasis. During autophagy, defective cargoes including mitochondria are targeted to lysosomes for cleara...

Microtubule-actin cross-linking factor 1 (MACF1) is a large protein of the spectraplakin family, which is essential for brain development. MACF1 inter…

Bastille and colleagues demonstrate that two closely related transcription factors, c-Maf and Mafb, have both redundant and independent effects on the diversification and functional differentiation of peripheral auditory neurons. Their data suggest that varying combinations of c-Maf and Mafb generate nuanced differences in synaptic structure and function.

Background Very long chain fatty acids (VLCFAs) are an integral component of myelin and the epidermal water barrier. Variants in genes encoding enzymes responsible for catalyzing the first and rate ...

Scientific Reports - Parp1 deletion rescues cerebellar hypotrophy in xrcc1 mutant zebrafish

DNA double strand break repair pathways ensure genome stability and prevent disease. Here the authors show that the actin nucleating factor DIAPH1 and γ-actin promote homologous recombination (HR)-dep...

Our results support an autosomal recessive SLK-related NDD and suggest abnormal cytoskeleton-mediated neuronal maturation as the underlying mechanism.

Bi-allelic UGGT1 variants cause a distinct congenital disorder of glycosylation (UGGT1-CDG) with variable severity, characterized by neurodevelopmental impairment, seizures, dysmorphic features, and m...

We identify bi-allelic variants in TRMT1, encoding a tRNA-modification enzyme, that cause intellectual disability and developmental delay. Functional studies in human cells and zebrafish provide insig...

We identify bi-allelic variants in the mitoribosomal large subunit encoded by MRPL49 as a cause of a pleiotropic presentation of hearing loss, ovarian failure, learning disability, and leukodystrophy ...

Abdel-Hamid et al. identified biallelic GTF3C3 variants in four individuals with neurodevelopmental disorders, including developmental delay/intellectual d

Kaiyrzhanov et al. provide a cumulative phenotype characterization of NADH-ubiquinone oxidoreductase 1 alpha subcomplex 13 (NDUFA13)-related disease descri

Sequencing 8 individuals with intellectual disability identified bi-allelic variants in KICS2, which encodes a component of the KICSTOR complex. A combination of in vitro and in vivo analyses demonstr...

Zhang et al. elucidate the targets of a tRNA modification enzyme family and identify unanticipated roles for a duplicated tRNA modification enzyme that can be uncoupled from its ancestral function. These findings uncover the molecular mechanisms by which tRNAs are dysregulated in human disorders caused by tRNA modification deficiency.

Copper is indispensable for various metabolic processes, notably mitochondrial respiration. In humans, copper homeostasis hinges on transporters such as copper transporter 1 (CTR1), encoded by the SLC...

Defects in DNA single-strand break repair are associated with neurodevelopmental and neurodegenerati

Nature Genetics - Elucidating the genomic basis of rare pediatric neurological diseases in Central Asia and Transcaucasia