Technical Note: Measuring the thickness of histological sections by detecting fluorescence intensity of embedding foam

Fluorescence intensity of embedding foam in paraffin blocks can be used to measure the thickness of histological microsections. We embedded samples of embedding foam and produced several microsections of varying thicknesses using routine processing and staining. Fluorescence intensity in the blue area of the embedding foam detected with a slide scanner was compared to absolute thickness as measured using confocal microscopy. Correlation analysis displayed a clear linear correlation with convincingly low prediction interval. The concept of measuring thickness of histological microsections by detecting fluorescence intensity of embedding foam is suggested as an approach to high-throughput measuring of histological sections applicable for a fully digitized pathology department. No acquisition of dedicated equipment is required and the method can be applied as a fully automated technique requiring no time consumption

Reassessment of Gene-Elusive Familial Dilated Cardiomyopathy Leading to the Discovery of a Homozygous AARS2 Variant—The Importance of Regular Reassessment of Genetic Findings

Background: AARS2 encodes the mitochondrial protein alanyl-tRNA synthetase 2 (MT-AlaRS), an important enzyme in oxidative phosphorylation. Variants in AARS2 have previously been associated with infantile cardiomyopathy. Case summary: A 4-year-old girl died of infantile-onset dilated cardiomyopathy (DCM) in 1996. Fifteen years later, her 21-year-old brother was diagnosed with DCM and ultimately underwent heart transplantation. Initial sequencing of 15 genes discovered no pathogenic variants in the brother at the time of his diagnosis. However, 9 years later re-screening in an updated screening panel of 129 genes identified a homozygous AARS2 (c.1774C > T) variant. Sanger sequencing of the deceased girl confirmed her to be homozygous for the AARS2 variant, while both parents and a third sibling were all found to be unaffected heterozygous carriers of the AARS2 variant. Discussion: This report underlines the importance of repeated and extended genetic screening of elusive families with suspected hereditary cardiomyopathies, as our knowledge of disease-causing mutations continuously grows. Although identification of the genetic etiology in the reported family would not have changed the clinical management, the genetic finding allows genetic counselling and holds substantial value in identifying at-risk relatives