Schizophrenia (SCZ) is a well-studied neuropsychiatric condition that has been shown to have a high degree of genetic heritability. Still, little data on the specific genetic risk variants associated with the disease exists. Classification of the SCZ phenotype into SCZ-related endophenotypes is a promising methodology to parse out and elucidate the specific genetic risk variants for each. Here, we present a series of 17 previously reported individuals and a new proband with similar SCZ-related neuropsychiatric characteristics and shared brain imaging findings. Unsurprisingly, these individuals shared classic psychiatric features of SCZ. Interestingly, we also identified shared neuropsychiatric features in this series of individuals that had not been highlighted previously. A consistently decreased IQ, memory impairment, sleep and speech disturbances, and attention deficits were commonly reported findings. The brain imaging findings among these individuals also consistently showed posterior vermis predominant cerebellar hypoplasia (CBLH-V). Most individuals' diagnoses were initially described as Dandy-Walker malformation; however, our independent review of imaging suggests a more consistent pattern of posterior vermis predominant cerebellar hypoplasia rather than true Dandy-Walker malformation. While the specific genetic risk variants for this endophenotype are yet to be described, the aim of this paper is to present the shared neuropsychiatric features and consistent, symmetrical brain image findings which suggest that this subset of individuals comprises an endophenotype of SCZ with a high genetic solve rate.
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http://dx.doi.org/10.1002/ajmg.a.63416 | DOI Listing |
Am J Hum Genet
January 2025
Institute of Medical Genetics and Applied Genomics, University of Tübingen, 72076 Tübingen, Germany; Center for Rare Disease, University of Tübingen, 72076 Tübingen, Germany; Genomics for Health in Africa (GHA), Africa-Europe Cluster of Research Excellence (CoRE).
Inborn errors of selenoprotein expression arise from deleterious variants in genes encoding selenoproteins or selenoprotein biosynthetic factors, some of which are associated with neurodegenerative disorders. This study shows that bi-allelic selenocysteine tRNA-specific eukaryotic elongation factor (EEFSEC) variants cause selenoprotein deficiency, leading to progressive neurodegeneration. EEFSEC deficiency, an autosomal recessive disorder, manifests with global developmental delay, progressive spasticity, ataxia, and seizures.
View Article and Find Full Text PDFJ AAPOS
December 2024
Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, Canada.
A 13-month-old boy presented to the pediatric ophthalmology clinic at BC Children's Hospital for strabismus assessment. On examination he had a right facial hemangioma, left ptosis, and left exotropia and hypotropia. Magnetic resonance imaging and magnetic resonance angiography of his head demonstrated posterior cerebral artery tortuosity producing mild mass effect on the left oculomotor nerve.
View Article and Find Full Text PDFCommun Biol
December 2024
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Brain-derived neurotrophic factor (BDNF) plays important roles in brain development and neural function. Constitutive knockout of the splicing regulator RBM4 reduces BDNF expression in the developing brain and causes cerebellar hypoplasia, an autism-like feature. Here, we show that Rbm4 knockout induced intron 6 retention of Hsf1, leading to downregulation of HSF1 protein and its downstream target BDNF.
View Article and Find Full Text PDFJ Bone Miner Res
December 2024
Paris Cité University, Reference center for skeletal dysplasia, INSERM UMR 1163, Imagine Institute, Necker Enfants Malades Hospital (AP-HP), Paris, France.
Chondrodysplasias with multiple dislocations are rare skeletal disorders characterized by hyperlaxity, joint dislocations, and growth retardation. Chondrodysplasias with multiple dislocations have been linked to pathogenic variants in genes encoding proteins involved in the proteoglycan biosynthesis. In this study, by exome sequencing analysis, we identified a homozygous nonsense variant (NM_001297654.
View Article and Find Full Text PDFGenet Med
December 2024
Genetics Department, Hospices Civils de Lyon, Lyon, France; Neuromyogene Institute, Pathology and Genetics of neuron and muscle, CNRS UMR 5261 INSERM U1315, University of Lyon - Université Claude Bernard Lyon 1, Lyon, France. Electronic address:
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