key: cord-1010177-6hoo4yxv authors: Węgrzyn, Grzegorz; Pierzynowska, Karolina; Pavone, Luigi Michele title: Editorial: Molecular Aspects of Mucopolysaccharidoses date: 2022-02-28 journal: Front Mol Biosci DOI: 10.3389/fmolb.2022.874267 sha: d703ea143734de51fb4e40655a13f71e3b306e34 doc_id: 1010177 cord_uid: 6hoo4yxv nan Communication and discussion of all valuable data connected to rare diseases, like MPS, are crucial elements for the development of a more complete understanding of these disorders. Low number of patients causes limitations of sources of important data, making each solid result especially valuable. This problem has been discussed by Sampayo-Cordero et al. who presented the deleterious effects of excluding results of non-randomized studies from systematic reviews. The authors demonstrated that such a strategy of selection of data in reviews may result in a loss of a considerable amount of information in MPS and most probably in other rare diseases. Different strategies for combining data from randomized and non-randomized studies were discussed, and important recommendation for including results of both these types of studies in systematic reviews on MPS was proposed which should allow to both avoid a selection bias and increase the representativeness of the results. Genotype-phenotype relationships are important issues when predicting severity of MPS disease in patients at the time of diagnosis, as proper prediction might be crucial to choose the most effective management which is still of low efficiency. Unfortunately, such relationships are often questionable, and the level of difficulty of extrapolation of our knowledge based on previously described cases and molecular data on biochemical effects of specific mutations is very high. In silico programs provide tools for analyses of mutations and their possible effects, however, their reliability is unclear, especially when missense variants are investigated. An interesting comparison of 33 such programs in studies on mutations occurring in the IDUA gene (causing MPS I) has been presented by Matte et al. They analyzed 586 missense mutations in this gene and found that the ClinPred algorithms gave the best sensitivity, specificity, accuracy, and kappa value for two criteria established by the authors. This can be an important suggestion for further analyses of mutations in MPS I and other types of this disease. et al.) in Russia and some neighbor countries. Since this is a large territory, such analyses are very valuable for understanding basic processes of the cause of the diseases, geographical distribution of patients, potential effects of the founder, and other mechanisms related to epidemiology of rare diseases. Moreover, the presented results indicated feasibility of the newborn screening procedures in the country and suggested optimal diagnostic tools in specific ethnic groups. Finally, the study by Brusius-Facchin et al. indicated usefulness of the Next Generation Sequencing (NGS) in detection of carriers of MPS II. This disease is the only example of the X-linked disorders among all MPS types. Thus, proper identification of female carriers is especially important. Moreover, the use of NGS allowed to detect mosaicism in mothers of MPS II patients which was more accurate than classical DNA sequencing. This can be recognized as an important methodological improvement in assessment of the risk of MPS II. In summary, the articles published in this special issue indicated important methodological optimizations for studies on molecular aspects of MPS and provided valuable epidemiological and genetic data on selected types of MPS. Thus, readers are encouraged to read details of these studies, and to follow the molecular aspects of MPS in their further investigations. a Summary on mucopolysaccharidoses I-IX was presented by Tomatsu et al. (2018) , MPS X has been discovered recently by Verheyen et al. (2022) , and MPS-plus-syndrome (MPSPS) was characterized recently by Vasilev et al. (2020) (note that an MPS plus-like syndrome has been described in patients with mutations in the VPS16 gene, coding for vacuolar protein sorting protein 16; Yıldız et al., 2021) . Frontiers in Molecular Biosciences | www.frontiersin.org February 2022 | Volume 9 | Article 874267 Epidemiology of Mucopolysaccharidoses Update Targeted Metabolomic Analysis of a Mucopolysaccharidosis IIIB Mouse Model Reveals an Imbalance of Branched-Chain Amino Acid and Fatty Acid Metabolism Proteomic Analysis of Mucopolysaccharidosis IIIB Mouse Brain Heparan Sulfate Proteoglycans in Viral Infection and Treatment: a Special Focus on SARS-CoV-2. Ijms Pathogenesis of Mucopolysaccharidoses, an Update Underestimated Aspect of Mucopolysaccharidosis Pathogenesis: Global Changes in Cellular Processes Revealed by Transcriptomic Studies Gene Expression-Related Changes in Morphologies of Organelles and Cellular Component Organization in Mucopolysaccharidoses Update in the Mucopolysaccharidoses Transcriptomic Analyses Suggest that Mucopolysaccharidosis Patients May Be Less Susceptible to COVID-19 Mucopolysaccharidoses Update Mucopolysaccharidosis-plus Syndrome Novel Subtype of Mucopolysaccharidosis Caused by Arylsulfatase K (ARSK) Deficiency Homozygous Missense VPS16 Variant Is Associated with a Novel Disease, Resembling Mucopolysaccharidosis-Plus Syndrome in Two Siblings All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication. All authors contributed equally to this paper by participating in discussions, writting and text editing. Work of GW and KP on MPS was supported by Fundacja Sanfilippo (Poland) and by National Science Center (Poland) (within grant no. 2017/25/B/NZ2/00414), and that of LP was supported by Cure Sanfilippo Foundation (United States). The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.