When is it MODY? Challenges in the Interpretation of Sequence Variants in MODY Genes.

When is it MODY? Challenges in the Interpretation of Sequence Variants in MODY Genes. Rev Diabet Stud. 2015 Fall-Winter;12(3-4):330-48 Authors: Althari S, Gloyn AL Abstract The genomics revolution has raised more questions than it has provided answers. Big data from large population-scale resequencing studies are increasingly deconstructing classic notions of Mendelian disease genetics, which support a simplistic correlation between mutational severity and phenotypic outcome. The boundaries are being blurred as the body of evidence showing monogenic disease-causing alleles in healthy genomes, and in the genomes of individu-als with increased common complex disease risk, continues to grow. In this review, we focus on the newly emerging challenges which pertain to the interpretation of sequence variants in genes implicated in the pathogenesis of maturity-onset diabetes of the young (MODY), a presumed mono-genic form of diabetes characterized by Mendelian inheritance. These challenges highlight the complexities surrounding the assignments of pathogenicity, in particular to rare protein-alerting variants, and bring to the forefront some profound clinical diagnostic implications. As MODY is both genetically and clinically heterogeneous, an accurate molecular diagnosis and cautious extrapolation of sequence data are critical to effective disease management and treatment. The biological and translational value of sequence information can on...
Source: Review of Diabetic Studies - Category: Endocrinology Tags: Rev Diabet Stud Source Type: research