Congenital Generalized Lipodystrophy, Type 4 (CGL4) Associated With Myopathy Due To Novel PTRF Mutations

Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by near total absence of body fat since birth with predisposition to insulin resistance, diabetes, hypertriglyceridemia, and hepatic steatosis. Three CGL loci, AGPAT2, BSCL2, and CAV1, have been identified previously. Recently, mutations in polymerase I and transcript release factor (PTRF) were reported in five Japanese patients presenting with myopathy and CGL (CGL4). We report novel PTRF mutations and detailed phenotypes of two male and three female patients with CGL4 belonging to two pedigrees of Mexican origin (CGL7100 and CGL178) and one pedigree of Turkish origin (CGL180). All patients had near total loss of body fat and congenital myopathy manifesting as weakness, percussion-induced muscle mounding, and high serum creatine kinase levels. Four of them had hypertriglyceridemia. Three of them had atlantoaxial instability. Two patients belonging to CGL178 pedigree required surgery for pyloric stenosis in the first month of life. None of them had prolonged QT interval on electrocardiography but both siblings belonging to CGL7100 had exercise-induced ventricular arrhythmias. Three of them had mild acanthosis nigricans but had normal glucose tolerance. Two of them had hepatic steatosis. All patients had novel null mutations in PTRF gene. In conclusion, mutations in PTRF result in a novel phenotype that includes generalized lipodystrophy with mild metabolic derangements, myopathy, cardiac arrhythmias, atlantoaxial instability, and pyloric stenosis. It is unclear how mutations in PTRF, which plays an essential role in formation of caveolae, affect a wide variety of tissues resulting in a variable phenotype. (C) 2010 Wiley-Liss, Inc

A telepathology based screening tool for COVID-19 by leveraging morphological changes related to leukocytes in peripheral blood smears

As we approach the aftermath of a global pandemic caused by Severe Acute Respiratory Syndrome-Corona Virus (SARS-CoV-2), the importance of quickly developing rapid screening tests has become very clear from the point of view of containment and also saving lives. Here, we present an explorative study to develop a telepathology-based screening tool using peripheral blood smears (PBS) to identify Coronavirus Disease (COVID-19)-positive cases from a group of 138 patients with flu-like symptoms, consisting of 82 positive and 56 negative samples. Stained blood smear slides were imaged using an automated slide scanner (AI 100) and the images uploaded to the cloud were analyzed by a pathologist to generate semi-quantitative leukocyte morphology-related data. These telepathology data were compared with the data generated from manual microscopy of the same set of smear slides and also the same pathologist. Besides good correlation between the data from telepathology and manual microscopy, we were able to achieve a sensitivity and specificity of 0.83 and 0.71, respectively, for identifying positive and negative COVID-19 cases using a six-parameter combination associated with leukocyte morphology. The morphological features included plasmacytoid cells, neutrophil dysplastic promyelocyte, neutrophil blast-like cells, apoptotic cells, smudged neutrophil, and neutrophil-to-immature granulocyte ratio. Although Polymerase Chain Reaction (PCR) and antibody tests have a superior performance, the PBS-based telepathology tool presented here has the potential to be an interim screening tool in resource-limited settings in underdeveloped and developing countries