RESUMO
Hypertrophic cardiomyopathy associated with damaging variants in the ALPK3 gene is a fairly recent discovery, and only a small number of patients have been described thus far. Here we present two additional patients with hypertrophic cardiomyopathy caused by biallelic variants in ALPK3. Genetic investigation was performed using a targeted gene panel consisting of known cardiomyopathy-associated genes and whole exome sequencing. The patients showed a large difference in the age of onset, and both presented with extracardiac features that are often seen in ALPK3 patients. The patient with the later onset showed milder extracardiac symptoms, such as decreased muscle tone and distal muscular dystrophy, but had fast progression of cardiac complications leading to the need of heart transplantation. This study further elucidates the variability of both symptoms and age of onset among these patients.
Assuntos
Cardiomiopatia Hipertrófica/patologia , Heterozigoto , Homozigoto , Proteínas Musculares/genética , Músculo Esquelético/patologia , Mutação , Proteínas Quinases/genética , Adulto , Idade de Início , Cardiomiopatia Hipertrófica/genética , Feminino , Humanos , Recém-Nascido , Masculino , Músculo Esquelético/metabolismo , Fenótipo , Sequenciamento do Exoma , Adulto JovemRESUMO
The microstructure and microhardness evolution of a Ti-15(wt.%)Mo/TiB metal-matrix composite (MMC) during high-pressure torsion (HPT) at 400 °C was studied. The composite was fabricated by spark plasma sintering of a Ti, Mo and TiB2 powders mixture at 1200 °C. In the initial condition, the structure of the composite consisted mainly of body-centered cubic (bcc) Ti solid solution and TiB whiskers. An increase in dislocation density, a considerable decrease in a grain size in the bcc Ti matrix, and breaking/rearrangement of the TiB whiskers were observed during HPT. The (sub)grain size in the bcc Ti matrix attained after 1 revolution was ~75 nm and then gradually decreased to ~55 nm after 5 revolutions. The TiB particle sizes after 5 revolutions was found to be 130â»210 nm. The microhardness increased with strain from 575 HV in the initial state to 730 HV after 5 revolutions. Various hardening mechanisms' contributions in the Ti-15Mo/TiB were evaluated.