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 […]
Early Newborn Metabolic Patterning and Sudden Infant Death Syndrome
JAMA Pediatr. 2024 Sep 9. doi: 10.1001/jamapediatrics.2024.3033. Online ahead of print. 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 […]
Parent and patient knowledge and attitudes about cancer predisposition syndrome genetic testing in pediatric oncology: Understanding sociodemographic and parent-child differences
Cancer Rep (Hoboken). 2024 Sep;7(9):e2119. doi: 10.1002/cnr2.2119. ABSTRACT BACKGROUND: Cancer predisposition syndromes (CPS) impact about 10% of patients with pediatric cancer. Genetic testing (CPS-GT) has multiple benefits, but few studies have described parent and child knowledge and attitudes regarding CPS-GT decision-making. This study examined parent and patient CPS-GT decision-making knowledge and attitudes. PROCEDURE: English- or […]
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 […]
Loss of symmetric cell division of apical neural progenitors drives DENND5A-related developmental and epileptic encephalopathy
Nat Commun. 2024 Aug 22;15(1):7239. doi: 10.1038/s41467-024-51310-z. ABSTRACT Developmental and epileptic encephalopathies (DEEs) feature altered brain development, developmental delay and seizures, with seizures exacerbating developmental delay. Here we identify a cohort with biallelic variants in DENND5A, encoding a membrane trafficking protein, and develop animal models with phenotypes like the human syndrome. We demonstrate that DENND5A […]