About this Research Topic
Studying rare pedigrees and atypical presentations of well-established phenotypes at both genetic and functional levels can bridge the existing knowledge gap, improving the applications of existing data. The molecular mechanisms underlying genetic conditions can be better understood by investigating the pathogenic effects of individual variants at the protein level. Since the type of mutation has differential effects at the expression level, the characterization of variant-specific consequences will provide basic grounds for explaining and understanding the general variabilities in genotype-phenotype correlation. Furthermore, such findings, in a broader spectrum, will also connect the dots in the complex cellular interactome of proteins. Optimistically, the characterization of single protein/protein complexes enriches our understanding of protein networks thereby increasing the potential for developing therapies for currently incurable rare diseases. By combining classical and state-of-the-art techniques for studying expression profiles, the pending questions regarding variabilities in genotype-phenotype correlation can be answered.
For this special issue, we welcome original articles, brief research reports, general commentary, hypothesis & theory, methods, opinions, perspectives, reviews, systematic reviews, and technology and code on large cohort studies informing about the identification of novel genes and the pathomechanisms of variants causing Mendelian disorders. We encourage articles showing assays for transcript/protein expression levels for specific mutational effects, localization, characterization of domains, protein-protein interactions, and investigation of protein chemistry. Minireviews and systematic reviews combining genetic findings and highlighting atypical clinical symptoms are also welcome.
Keywords: Mendelian Disorders, Embryonic development, Next-generation sequencing, Disease-gene discovery, Pathomechanism
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