Highlighted Publications

This month’s highlighted publication in Nature Genetics explores how inaccurate naming of genetic variants is contributing to the misdiagnosis and delayed diagnosis of rare genetic diseases. Led by Dr. Peter Freeman from The University of Manchester, the study reveals that around 6,000 UK children with rare genetic disorders go undiagnosed each year, with many dying without the underlying cause being identified.

The research underscores the widespread use of outdated or non-standard naming systems by clinicians, which obstructs the identification of relevant genetic data in key databases like ClinVar and the Leiden Open Variation Database (LOVD). This inconsistency prevents geneticists from accessing crucial information, even when it exists in the literature, slowing down diagnoses and negatively affecting patient care.

To address these issues, Freeman and his team developed VariantValidator, an open-source tool that standardizes variant descriptions according to the Human Genome Variation Society (HGVS) naming guidelines. The tool is already considered the gold standard for variant naming and is being adopted by leading medical journals to improve the accuracy of diagnostic data sharing across clinical and research platforms.

The study calls for widespread adoption of VariantValidator to ensure diagnostic precision and avoid misdiagnoses. It also highlights the financial cost of diagnostic delays, estimating that the NHS spends over £3 billion each decade on prolonged diagnostic journeys for rare diseases.

Reference:

Freeman PJ, Wagstaff JF, Fokkema IFAC, Cutting GR, Rehm HL, Davies AC, den Dunnen JT, Gretton LJ, Dalgleish R. Standardizing variant naming in literature with VariantValidator to increase diagnostic rates. Nat Genet. 2024 Oct. doi: 10.1038/s41588-024-01938-w.