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 […]
Early Newborn Metabolic Patterning and Sudden Infant Death Syndrome
Abstract Importance: Sudden infant death syndrome (SIDS) is a major cause of infant death in the US. Previous research suggests that inborn errors of metabolism may contribute to SIDS, yet the relationship between SIDS and biomarkers of metabolism remains unclear. Objective: To evaluate and model the association between routinely measured newborn metabolic markers and SIDS […]
Treating the Untreatable: Antisense Oligonucleotides as an Individualized Therapy for Rare Genetic Kidney Disease
J Am Soc Nephrol. 2024 Sep 27. doi: 10.1681/ASN.0000000532. Online ahead of print. NO ABSTRACT PMID:39331470 | DOI:10.1681/ASN.0000000532
The Face and Features of RNU4-2: A New, Common, Recognizable, Yet Hidden Neurodevelopmental Disorder
Pediatr Neurol. 2024 Sep 21;161:188-193. doi: 10.1016/j.pediatrneurol.2024.09.015. Online ahead of print. ABSTRACT BACKGROUND: RNU4-2 is a newly identified, noncoding gene responsible for a significant proportion of individuals with neurodevelopmental disorders (NDDs). Diagnosis is hampered by the inability of commonly employed clinical testing methods, including exome sequencing and currently formulated multigene panels, to detect variants in […]
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 […]
Autosomal recessive VWA1-related disorder: comprehensive analysis of phenotypic variability and genetic mutations
Brain Commun. 2024 Oct 28;6(6):fcae377. doi: 10.1093/braincomms/fcae377. eCollection 2024. ABSTRACT A newly identified subtype of hereditary axonal motor neuropathy, characterized by early proximal limb involvement, has been discovered in a cohort of 34 individuals with biallelic variants in von Willebrand factor A domain-containing 1 (VWA1). This study further delineates the disease characteristics in a cohort […]
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 […]
Elucidating the clinical and genetic spectrum of inositol polyphosphate phosphatase INPP4A-related neurodevelopmental disorder
Genet Med. 2024 Sep 20:101278. doi: 10.1016/j.gim.2024.101278. Online ahead of print. ABSTRACT PURPOSE: Biallelic INPP4A variants have recently been associated with severe neurodevelopmental disease in single case reports. Here, we expand and elucidate the clinical-genetic spectrum and provide a pathomechanistic explanation for genotype-phenotype correlations. METHODS: Clinical and genomic investigations of 30 individuals were undertaken alongside […]
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 […]