Testing and reporting ACMG cystic fibrosis mutation panel results

Area of Science:

• Medical Genetics
• Genetic Testing
• Cystic Fibrosis Research

Background:

• Cystic Fibrosis (CF) diagnosis relies on genetic testing, but interpretation of results can be complex, especially for pregnant or symptomatic individuals.
• Existing testing panels may not cover all scenarios, necessitating refined strategies for accurate risk assessment.

Purpose of the Study:

• To develop and define testing strategies and summary reports for cystic fibrosis (CF) genetic testing in pregnant and symptomatic patients.
• To establish the proportion of CFTR mutations detected by the ACMG-recommended 23-mutation panel across various patient categories.

Main Methods:

• Calculated posterior test risk tables incorporating patient/family history, ethnicity, and prior testing status.
• Utilized the American College of Medical Genetics (ACMG)-recommended 23-mutation CFTR gene panel for mutation detection.
• Developed reference tables for prior and posterior test risks to cover >99% of tested cases.

Main Results:

• Defined mutation detection rates for the 23-mutation CFTR panel across diverse patient groups, including pregnant couples and CF patients.
• Created comprehensive risk tables (prior and posterior) to aid in reporting results according to HIPAA guidelines.
• Demonstrated that negative results for one partner with no family history on the 23-mutation panel indicate no further prenatal testing is needed.

Conclusions:

• Developed robust testing strategies and risk assessment tools for CF genetic screening.
• The 23-mutation CFTR panel, when used with risk tables, effectively guides testing and reporting for most patient scenarios.
• These strategies enhance the accuracy and efficiency of cystic fibrosis genetic testing, particularly in prenatal and symptomatic cases.