Genetic screening for low-penetrance variants in protein-coding genes.

Area of Science:

• Genetics and Genomics
• Medical Screening
• Public Health

Background:

• Genetic testing aims to identify presymptomatic disease risk.
• Low-penetrance mutations present challenges due to variable disease manifestation.
• Population-based screening for these mutations is complex and debated.

Discussion:

• Medical expert panels frequently advise against screening for low-penetrance mutations because of high false-positive rates.
• Existing recommendations for genetic screening of low-penetrance mutations are limited.
• Case studies reviewed include glucose-6-phosphate dehydrogenase deficiency, cystic fibrosis, Gaucher disease, and hemochromatosis.

Key Insights:

• Screening for low-penetrance mutations is complex, with expert panels often recommending restricted use.
• Despite expert caution, genetic tests for low-penetrance mutations are increasingly accessible via direct-to-consumer channels.
• Balancing potential benefits against risks like false positives is crucial for clinical utility.

Outlook:

• Further research is needed to clarify the clinical utility and cost-effectiveness of screening for low-penetrance mutations.
• Development of clear guidelines for genetic testing of low-penetrance mutations is essential.
• The increasing availability of direct-to-consumer genetic testing necessitates informed public discourse and regulatory oversight.