Biallelic variants in GTF3C3 result in an autosomal recessive disorder with intellectual disability
Genet Med. 2024 Nov 7:101253. doi: 10.1016/j.gim.2024.101253. Online ahead of print. ABSTRACT PURPOSE: This study details a novel syndromic form of autosomal recessive intellectual disability resulting from recessive variants in GTF3C3, encoding a key component of the DNA-binding transcription factor IIIC, which has a conserved role in RNA polymerase III-mediated transcription. METHODS: Exome sequencing, minigene […]
Monoallelic loss-of-function variants in GSK3B lead to autism and developmental delay
Mol Psychiatry. 2024 Oct 29. doi: 10.1038/s41380-024-02806-z. Online ahead of print. ABSTRACT De novo variants adjacent to the canonical splicing sites or in the well-defined splicing-related regions are more likely to impair splicing but remain under-investigated in autism spectrum disorder (ASD). By analyzing large, recent ASD genome sequencing cohorts, we find a significant burden of […]
Clinical factors associated with genetic diagnosis in suspected neurogenetic disorders in a tertiary care clinic
Genet Med. 2024 Oct 10:101252. doi: 10.1016/j.gim.2024.101252. Online ahead of print. ABSTRACT PURPOSE: This study aimed to identify phenotypic factors associated with genetic diagnoses in patients with neurodevelopmental disorders and generate a decision tree to assist clinicians in identifying patients most likely to receive a positive result on genetic testing. METHODS: We retrospectively reviewed the […]
Clinical and Molecular Profiles of a Cohort of Egyptian Patients with Collagen VI-Related Dystrophy
J Mol Neurosci. 2024 Oct 5;74(4):93. doi: 10.1007/s12031-024-02266-8. ABSTRACT Collagen VI-related dystrophies (COL6-RD) display a wide spectrum of disease severity and genetic variability ranging from mild Bethlem myopathy (BM) to severe Ullrich congenital muscular dystrophy (UCMD) and the intermediate severities in between with dual modes of inheritance, dominant and recessive. In the current study, next-generation […]
Clinical and genetic delineation of autosomal recessive and dominant ACTL6B-related developmental brain disorders
Genet Med. 2024 Sep 10:101251. doi: 10.1016/j.gim.2024.101251. Online ahead of print. ABSTRACT PURPOSE: This study aims to comprehensively delineate the phenotypic spectrum of ACTL6B-related disorders, previously associated with both autosomal recessive and autosomal dominant neurodevelopmental disorders. Molecularly, the role of the nucleolar protein ACTL6B in contributing to the disease has remained unclear. METHODS: We identified […]
Clinical and neuroradiological spectrum of biallelic variants in NOTCH3
EBioMedicine. 2024 Aug 26;107:105297. doi: 10.1016/j.ebiom.2024.105297. Online ahead of print. ABSTRACT BACKGROUND: NOTCH3 encodes a transmembrane receptor critical for vascular smooth muscle cell function. NOTCH3 variants are the leading cause of hereditary cerebral small vessel disease (SVD). While monoallelic cysteine-involving missense variants in NOTCH3 are well-studied in cerebral autosomal dominant arteriopathy with subcortical infarcts and […]
Antisense oligonucleotide therapy in an individual with KIF1A-associated neurological disorder
Nat Med. 2024 Aug 9. doi: 10.1038/s41591-024-03197-y. Online ahead of print. ABSTRACT KIF1A-associated neurological disorder (KAND) is a neurodegenerative and often lethal ultrarare disease with a wide phenotypic spectrum associated with largely heterozygous de novo missense variants in KIF1A. Antisense oligonucleotide treatments represent a promising approach for personalized treatments in ultrarare diseases. Here we report […]
MSL2 variants lead to a neurodevelopmental syndrome with lack of coordination, epilepsy, specific dysmorphisms, and a distinct episignature
Am J Hum Genet. 2024 May 28:S0002-9297(24)00164-2. doi: 10.1016/j.ajhg.2024.05.001. Online ahead of print. ABSTRACT Epigenetic dysregulation has emerged as an important etiological mechanism of neurodevelopmental disorders (NDDs). Pathogenic variation in epigenetic regulators can impair deposition of histone post-translational modifications leading to aberrant spatiotemporal gene expression during neurodevelopment. The male-specific lethal (MSL) complex is a prominent […]
Sunflower Syndrome: A Survey of Provider Awareness and Management Preferences
Pediatr Neurol. 2023 Nov 30;152:177-183. doi: 10.1016/j.pediatrneurol.2023.11.013. Online ahead of print. ABSTRACT BACKGROUND: Sunflower syndrome is a rare photosensitive pediatric epilepsy characterized by stereotyped hand-waving in response to bright lights. These stereotyped movements with maintained awareness can be mistaken for a movement disorder. This study assessed neurology providers’ diagnostic reasoning, evaluation, and treatment of Sunflower […]
ARF1-related disorder: phenotypic and molecular spectrum
J Med Genet. 2023 Apr 25:jmg-2022-108803. doi: 10.1136/jmg-2022-108803. Online ahead of print. ABSTRACT PURPOSE: ARF1 was previously implicated in periventricular nodular heterotopia (PVNH) in only five individuals and systematic clinical characterisation was not available. The aim of this study is to provide a comprehensive description of the phenotypic and genotypic spectrum of ARF1-related neurodevelopmental disorder. […]