Comprehensive Genotypic, Phenotypic, and Biochemical Characterization of GOT2 Deficiency: A Progressive Neurodevelopmental Disorder with Epilepsy and Abnormal Movements
Genet Med. 2025 Sep 22:101587. doi: 10.1016/j.gim.2025.101587. Online ahead of print. ABSTRACT PURPOSE: Glutamic-oxaloacetic transaminase (GOT), also known as aspartate aminotransferase, catalyzes the reversible transamination of oxaloacetate and glutamate to aspartate and α-ketoglutarate. Two isoforms, cytosolic (GOT1) and mitochondrial (GOT2), are integral to the malate-aspartate shuttle (MAS), a key regulator of intracellular redox homeostasis. Recently, […]
PIGC-related encephalopathy: Lessons learned from 18 new probands
Eur J Hum Genet. 2025 Sep 17. doi: 10.1038/s41431-025-01923-9. Online ahead of print. ABSTRACT PIGC encodes a protein essential for the biosynthesis of glycophosphatidylinositol-anchored proteins (GPI-APs). So far, three families with biallelic PIGC variants have been reported to exhibit developmental delay/intellectual disability and seizures. Our aim was to further elucidate the clinical and biomolecular characteristics […]
A clinical and genotype-phenotype analysis of MACF1 variants
Am J Hum Genet. 2025 Sep 3:S0002-9297(25)00320-9. doi: 10.1016/j.ajhg.2025.08.010. Online ahead of print. ABSTRACT Microtubule-actin cross-linking factor 1 (MACF1) is a large protein of the spectraplakin family, which is essential for brain development. MACF1 interacts with microtubules through the growth arrest-specific 2 (Gas2)-related (GAR) domain. Heterozygous MACF1 missense variants affecting the zinc-binding residues in this […]
Essential genetic testing in movement disorders – results from a Delphi study
Parkinsonism Relat Disord. 2026 May 22;148:108367. doi: 10.1016/j.parkreldis.2026.108367. Online ahead of print. ABSTRACT BACKGROUND: While genetic testing in Movement Disorders (MD) has expanded enormously, access to genetic testing and genetic counseling remains asymmetric at the global scale. Guidance on efficient testing strategies for clinicians, governments and stakeholders is crucial. OBJECTIVES: Establish a list of genetic […]
Expanding the Phenotype of Syndromic SLC30A9-Associated Disease
Am J Med Genet A. 2025 Nov 26:e70007. doi: 10.1002/ajmga.70007. Online ahead of print. ABSTRACT SLC30A9 mutations are linked to Birk-Landau-Perez syndrome, which is characterized by neurodevelopmental and renal disease, thought to result from impaired zinc homeostasis. In this report, we describe a patient with a homozygous likely pathogenic SLC30A9 variant with atypical chorio-retinal degeneration, […]
A phenotypic brain organoid atlas and biobank for neurodevelopmental disorders
Cell Stem Cell. 2025 Nov 3:S1934-5909(25)00374-1. doi: 10.1016/j.stem.2025.10.006. Online ahead of print. ABSTRACT Thousands of genes are associated with neurodevelopmental disorders (NDDs), yet mechanisms and targeted treatments remain elusive. To fill these gaps, we present a California Institute of Regenerative Medicine (CIRM)-initiated NDD biobank of 352 publicly available genetically diverse patient-derived induced pluripotent stem cells […]
Splicing and frameshift variants in QSER1 may be involved in developmental phenotypes
HGG Adv. 2025 Oct 25:100539. doi: 10.1016/j.xhgg.2025.100539. Online ahead of print. ABSTRACT Human development is a complex process that requires precise control of gene expression through regulatory proteins. Recently, heterozygous variants in PRR12, encoding a proline-rich regulatory protein, were found to cause a variable phenotype involving developmental delay/cognitive impairment, neuropsychiatric diagnoses, structural eye anomalies, congenital […]
ACTB deletions or single-nucleotide loss-of-function variants: expansion and further delineation of the phenotype and review of the literature
J Med Genet. 2025 Oct 8:jmg-2025-110631. doi: 10.1136/jmg-2025-110631. Online ahead of print. ABSTRACT BACKGROUND: Pathogenic gain-of-function or dominant-negative effect missense variations in ACTB are associated with a neurodevelopmental disorder characterised by intellectual disability (ID), seizures, sensorineural hearing loss, cerebral, renal and ocular abnormalities and dysmorphic features (Baraitser-Winter cerebrofrontofacial syndrome). ACTB encodes beta-actin, a highly conserved […]