11 research outputs found
Increased Burden of Rare Protein-Truncating Variants in Constrained, Brain-specific and Synaptic Genes In Extremely Impulsively Violent Males with Antisocial Personality Disorder
Mutations in ANTXR1 Cause GAPO Syndrome
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116575.pdf (publisher's version ) (Closed access)The genetic cause of GAPO syndrome, a condition characterized by growth retardation, alopecia, pseudoanodontia, and progressive visual impairment, has not previously been identified. We studied four ethnically unrelated affected individuals and identified homozygous nonsense mutations (c.262C>T [p.Arg88(*)] and c.505C>T [p.Arg169(*)]) or splicing mutations (c.1435-12A>G [p.Gly479Phefs(*)119]) in ANTXR1, which encodes anthrax toxin receptor 1. The nonsense mutations predictably trigger nonsense-mediated mRNA decay, resulting in the loss of ANTXR1. The transcript with the splicing mutation theoretically encodes a truncated ANTXR1 containing a neopeptide composed of 118 unique amino acids in its C terminus. GAPO syndrome's major phenotypic features, which include dental abnormalities and the accumulation of extracellular matrix, recapitulate those found in Antxr1-mutant mice and point toward an underlying defect in extracellular-matrix regulation. Thus, we propose that mutations affecting ANTXR1 function are responsible for this disease's characteristic generalized defect in extracellular-matrix homeostasis.8 p
<em>POLRMT </em>mutations impair mitochondrial transcription causing neurological disease
Mutations in PNPLA6 are linked to photoreceptor degeneration and various forms of childhood blindness
Mutations in PNPLA6 are linked to photoreceptor degeneration and various forms of childhood blindness
Meta-analysis of the diagnostic and clinical utility of genome and exome sequencing and chromosomal microarray in children with suspected genetic diseases
How Cardiac Cytoarchitecture Can Go Wrong: Hypertrophic Cardiomyopathy as a Paradigm for Genetic Disease of the Heart
When signalling goes wrong: pathogenic variants in structural and signalling proteins causing cardiomyopathies
Cardiomyopathies are a diverse group of cardiac disorders with distinct phenotypes, depending on the proteins and pathways affected. A substantial proportion of cardiomyopathies are inherited and those will be the focus of this review article. With the wide application of high-throughput sequencing in the practice of clinical genetics, the roles of novel genes in cardiomyopathies are recognised. Here, we focus on a subgroup of cardiomyopathy genes [TTN, FHL1, CSRP3, FLNC and PLN, coding for Titin, Four and a Half LIM domain 1, Muscle LIM Protein, Filamin C and Phospholamban, respectively], which, despite their diverse biological functions, all have important signalling functions in the heart, suggesting that disturbances in signalling networks can contribute to cardiomyopathies.</p