Machine-Readable Database for Genotype-Phenotype Analyses in Rare Diseases Using FKTN-related Congenital Muscular Dystrophies as a Prototype.

The FKTN -related muscular dystrophies are a subtype of highly heterogeneous, ultra-rare genetic diseases that are part of the α-dystroglycanopathies (αDGs). These disorders present with different prevalences depending on the population and cause a spectrum of severities with frequently severe phenotypes with often congenital presentation (congenital muscular dystrophy). To better understand the impact of specific FKTN variants in the affected individuals, we first comprehensively aggregated all publicly known and available data resulting in a database comprising all published literature that details FKTN variants and their associated clinical phenotypes. A machine-readable format for the database was achievedvia harmonized data conversion for genotypes and clinical phenotypes. We also developed a clinical severity scale utilizing previously existing metrics as a means of categorizing phenotypic data to facilitate effective genotype/phenotype correlation. This dataset also serves as a pilot for similar data extraction and harmonization in other muscular dystrophies and rare monogenic diseases.