Beyond Mutation: Exploring the Molecular Genetics and Pathomechanisms of Mendelian Disorders

The field of molecular genetics has long been focused on unraveling the complexities of the human genome, particularly through the study of Mendelian disorders. These disorders, which arise from single-gene mutations, offer a unique window into the functional aspects of our genetic code. Recent advancements in genomic technologies have significantly accelerated the discovery of genetic variants associated with these conditions. However, the ability to classify these variants and elucidate their pathomechanisms remains a significant challenge. Despite extensive global efforts, the etiology of many rare phenotypes remains poorly understood. This gap highlights the necessity of not only identifying genetic variants but also exploring their specific effects at the transcript and protein levels. Addressing these gaps can enhance our understanding of genotype-phenotype correlations and improve diagnostic and prognostic capabilities.

This research topic aims to delve into the molecular genetics and pathomechanisms of Mendelian disorders. The primary objective is to identify and characterize genetic variants and understand their specific effects on protein expression and function. By investigating the pathogenic effects of individual variants, this research seeks to bridge the existing knowledge gap and provide a more comprehensive understanding of the molecular mechanisms underlying these genetic conditions. Key questions include how different types of mutations affect protein expression and function, and how these effects contribute to the variability in clinical presentations.

To gather further insights into the molecular genetics and pathomechanisms of Mendelian disorders, we welcome articles addressing, but not limited to, the following themes:

• Identification of novel genes associated with Mendelian disorders
• Pathomechanisms of genetic variants at the transcript and protein levels
• Assays for transcript/protein expression levels for specific mutational effects
• Localization and characterization of protein domains
• Protein-protein interactions and their implications in disease
• Investigation of protein chemistry and its role in pathogenesis
• Large cohort studies informing genetic findings
• Reviews and systematic reviews highlighting atypical clinical symptoms and genetic findings

By combining classical and state-of-the-art techniques, this research topic aims to answer pending questions regarding variabilities in genotype-phenotype correlations and pave the way for developing therapies for currently incurable rare diseases.

Keywords: Mendelian Disorders, Embryonic development, Next-generation sequencing, Disease-gene discovery, Pathomechanism

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.