Detection of disease-causing CFTR variants in state newborn screening programs

Area of Science:

• Genetics and genomics
• Public health
• Medical diagnostics

Background:

• Newborn screening (NBS) for cystic fibrosis (CF) utilizes varying cystic fibrosis transmembrane conductance regulator (CFTR) variant panels across the US.
• CFTR variant distribution differs significantly among racial and ethnic populations.

Purpose of the Study:

• To compare CFTR variant panel detection rates across different racial and ethnic groups.
• To identify state-specific detection rates for CFTR variant panels.
• To analyze rates of false-negative NBS and delayed CF diagnoses by race and ethnicity.

Main Methods:

• Cross-sectional analysis of CFTR variant detection rates in genotyped individuals with CF or CFTR-related disorders (CRMS/CFTR-related disorders) from the 2020 CF Foundation Patient Registry (CFFPR).
• Estimation of case detection rates by applying panel data to US Census demographics.
• Comparison of delayed diagnosis and false-negative NBS rates by race and ethnicity using CFFPR data.

Main Results:

• Detection of at least one CFTR variant was highest in non-Hispanic White individuals (87.5%-97.0%) and lowest in Black, Asian, and Hispanic individuals (41.9%-93.1%).
• Lower detection rates were observed in Black and Asian individuals with CRMS/CFTR-related disorders (48.4%-64.8%).
• States with greater racial and ethnic diversity exhibited lower detection rates for all panels. Black, Hispanic, and mixed-race individuals were overrepresented in false-negative NBS (3.8%) and delayed diagnoses (11.8%).

Conclusions:

• CFTR variant panels demonstrate reduced detection efficacy in minoritized racial and ethnic groups.
• These disparities contribute to an increased risk of false-negative NBS and delayed CF diagnoses.
• The findings highlight potential health inequities stemming from current NBS strategies.