Akt3 links mitochondrial function to the regulation of Aurora B and mitotic fidelity.

Akt3 is a key regulator of mitochondrial homeostasis in the endothelium. Akt3 depletion results in mitochondrial dysfunction, decreased mitochondrial biogenesis, and decreased angiogenesis. Here we link mitochondrial homeostasis with mitotic fidelity-depletion of Akt3 results in the missegregation of chromosomes as visualized by multinucleation and micronuclei formation.

Taking on the Titin: Muscle imaging as a diagnostic marker of biallelic related myopathy.

Background: The accurate diagnosis of titin-related myopathies (-RM) is challenging due to the "gigantism" of the coding gene with an incompletely understood landscape of normal genetic variation, an increasing number of pathogenic variants, and wide phenotypic variability of both cardiac and muscle involvement. Particularly in situations of potentially incomplete genotypes, clinicians need more phenotyping tools to help confidently determine the pathogenicity of variants in and accurately diagnose titinopathies.

Objective: To illustrate the pattern of muscle involvement found by muscle imaging in patients with RM.

Clinical characterization of Collagen XII-related disease caused by biallelic COL12A1 variants.

Objective: While there have been several reports of patients with dominantly acting COL12A1 variants, few cases of the more severe recessive Collagen XII-related disorders have previously been documented.

Methods: We present detailed clinical, immunocytochemical, and imaging data on eight additional patients from seven families with biallelic pathogenic variants in COL12A1.

Results: All patients presented with a consistent constellation of congenital onset clinical features: hypotonia, dysmorphic features, most notably gingival hypertrophy, prominent distal joint hyperlaxity, with co-occurring contractures of large joints, and variable muscle involvement, evident both clinically and on muscle imaging.

Effects of HMG CoA reductase (HMGCR) deficiency on skeletal muscle development.

Pathogenic variants in HMGCR were recently linked to a limb-girdle muscular dystrophy (LGMD) phenotype. The protein product HMG CoA reductase (HMGCR) catalyzes a key component of the cholesterol synthesis pathway. The two other muscle diseases associated with HMGCR, statin-associated myopathy (SAM) and autoimmune anti-HMGCR myopathy, are not inherited in a Mendelian pattern.

A study to identify individuals at risk to be affected by late-onset Pompe disease who had previously been given a non-specific or tentative diagnosis for their muscle weakness (Pompe PURSUE).

Background: Late-onset Pompe disease (LOPD) is an autosomal recessive lysosomal storage disorder that results in severe progressive proximal muscle weakness. Over time, reductions in muscle strength result in respiratory failure and a loss of ambulation. Delayed diagnosis of LOPD deprives patients of treatments that can enhance quality of life and potentially slow disease progression.