Parental mosaicism in Marfan and Ehlers-Danlos syndromes and related disorders.

Marfan syndrome (MFS) is a heritable connective tissue disorder (HCTD) caused by pathogenic variants in FBN1 that frequently occur de novo. Although individuals with somatogonadal mosaicisms have been reported with respect to MFS and other HCTD, the overall frequency of parental mosaicism in this pathology is unknown. In an attempt to estimate this frequency, we reviewed all the 333 patients with a disease-causing variant in FBN1. We then used direct sequencing, combined with High Resolution Melting Analysis, to detect mosaicism in their parents, complemented by NGS when a mosaicism was objectivized. We found that (1) the number of apparently de novo events is much higher than the classically admitted number (around 50% of patients and not 25% as expected for FBN1) and (2) around 5% of the FBN1 disease-causing variants were not actually de novo as anticipated, but inherited in a context of somatogonadal mosaicisms revealed in parents from three families. High Resolution Melting Analysis and NGS were more efficient at detecting and evaluating the level of mosaicism compared to direct Sanger sequencing. We also investigated individuals with a causal variant in another gene identified through our "aortic diseases genes" NGS panel and report, for the first time, on an individual with a somatogonadal mosaicism in COL5A1. Our study shows that parental mosaicism is not that rare in Marfan syndrome and should be investigated with appropriate methods given its implications in patient's management.

A +3 variant at a donor splice site leads to a skipping of the MYH11 exon 32, a recurrent RNA defect causing Heritable Thoracic Aortic Aneurysm and Dissection and/or Patent Ductus Arteriosus.

BACKGROUND: Pathogenic variants in MYH11 are associated with either heritable thoracic aortic aneurysm and dissection (HTAAD), patent ductus arteriosus (PDA) syndrome, or megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS). METHODS AND RESULTS: We report a family referred for molecular diagnosis with HTAAD/PDA phenotype in which we found a variant at a non-conserved position of the 5' donor splice site of intron 32 of MYH11 potentially altering splicing (NM_002474.3:c.4578+3A>C). Although its cosegregation with disease was observed, it remained of unknown significance. Later, aortic surgery in the proband gave us the opportunity to perform a transcript analysis. This showed a skipping of the exon 32, an RNA defect previously reported to be translated to an in-frame loss of 71 amino acids and a dominant-negative effect in the smooth muscle myosin rod. This RNA defect is also reported in 3 other HTAAD/PDA pedigrees. CONCLUSION: This report confirms that among rare variants in MYH11, skipping of exon 32 is recurrent. This finding is of particular interest to establish complex genotype-phenotype correlations where some alleles are associated with autosomal dominant HTAAD/PDA, while others result in recessive or dominant visceral myopathies.

Reliable chiral recognition with an optoelectronic nose.

Chiral discrimination is a key problem in analytical chemistry. It is generally performed using expensive instruments or highly-specific miniaturized sensors. An electronic nose is a bio-inspired instrument capable after training of discriminating a wide variety of analytes. However, generality is achieved at the cost of specificity which makes chiral recognition a challenging task for this kind of device. Recently, a peptide-based optoelectronic nose which can board up to hundreds of different sensing materials has shown promising results, especially in terms of specificity. In line with these results, we describe here its use for chiral recognition. This challenging task requires care, especially in terms of statistical reliability and experimental confounds. For these reasons, we set up an automatic gas sampling system and recorded data over two long sessions, taking care to exclude possible confounds. Two couples of chiral molecules, namely (R) and (S) Limonene and (R) and (S) Carvone, were tested and several statistical analyses indicate the almost perfect discrimination of their two enantiomers. A method to highlight discriminative sensing materials is also proposed and shows that successful discrimination is likely achieved using just a few peptides.

Local variation within marinas: Effects of pollutants and implications for invasive species.

Urban structures like marinas are dominant features of our coasts, often hotspots for invasive species. The processes that govern the distribution of invasive species within and between marinas are not well understood. We therefore investigated the impacts of local-scale variability within and between marinas, analysing fouling communities at two zones (inner and outer) within three close marinas in accordance with pollutants recorded in the water and sediment. Communities varied between zones, however no significant differences in abundances of invasive species was recorded. The inner zones contained higher levels of copper and other pollutants and were correlated with lower biodiversity and abundances of many species in comparison to the outer zones. Only the native Ascidiella aspersa was found in greater abundances in the inner zones. This local-scale variability and how it impacts biodiversity is important for consideration for coastal managers in mitigating the build-up of pollutants and spread of invasive species.