Identification of CFTR variants in Latino patients with cystic fibrosis from the Dominican Republic and Puerto Rico

Self Cite

Background: Newborn screening (NBS) algorithms for cystic fibrosis (CF) vary in the United State of America and include different cystic fibrosis transmembrane conductance regulator (CFTR) variants. CFTR variant distribution varies among racial and ethnic groups. Objective: Our objectives were to identify differences in detection rate by race and ethnicity for CFTR variant panels, identify each US state detection rate for CFTR variant panels, and describe the rate of false-negative NBS and delayed diagnoses by race and ethnicity. Methods: This is a cross-sectional analysis of the detection rate of at least 1 CFTR variant for seven panels by race and ethnicity in genotyped people with CF (PwCF) or CFTR-related metabolic syndrome (CRMS)/CFTR-related disorders in CF Foundation Patient Registry (CFFPR) in 2020. We estimated the case detection rate of CFTR variant panels by applying the detection rate to Census data. Using data from CFFPR, we compared the rate of delayed diagnosis or false-negative NBS by race and ethnicity.Results: For all panels, detection of at least 1 CFTR variant was highest in non-Hispanic White PwCF (87.5%−97.0%), and lowest in Black, Asian, and Hispanic PwCF (41.9%−93.1%). Detection of at least 1 CFTR variant was lowest in Black and Asian people with CRMS/CFTR-related disorders (48.4%−64.8%). States with increased racial and ethnic diversity have lower detection rates for all panels.Overall, 3.8% PwCF had a false-negative NBS and 11.8% had a delayed diagnosis; Black, Hispanic, and mixed-race PwCF were overrepresented. Conclusion:CFTR variant panels have lower detection rates in minoritized racial and ethnic groups leading to false-negative NBS, delayed diagnosis, and likely health disparities.

“…For example, Hispanic populations have different CFTR variant type and frequency, even when closely geographically located. 35 | 471…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

McGarry

Ren

et al. 2022

Self Cite

“…While delF508 is the most common mutation in all groups, patients of a minority group are less likely to have a copy of delF508 and are more likely to have a deletion or duplication mutation, which can be missed when only DNA panels are used for CFTR mutation detection. Mutation frequency is not even uniform within patients of a minority group, 16 for example, it varies among Hispanic populations in different geographic locations 17 . There is no equity in mutation detection in patients of a minority group and non‐Hispanic White patients with CF.…”

Section: Discussionmentioning

confidence: 99%

“…Mutation frequency is not even uniform within patients of a minority group, 16 for example, it varies among Hispanic populations in different geographic locations. 17 There is no equity in mutation detection in patients of a minority group and non-Hispanic White patients with CF. Patients of a minority group are more likely to have unknown CFTR mutations; unknown CFTR mutations are associated with mortality in children with CF.…”

Section: Pulmonary Function By Eligibility and Cftr Modulator Prescriptionmentioning

confidence: 99%

“…Overall, approximately 90% of patients with CF have CFTR mutations that are currently FDA‐approved for CFTR modulators, although this may not be true for all groups within the CF population 14,15 . CF occurs in all racial and ethnic populations, though incidence and CFTR mutation prevalence varies by both geographic region and ancestry 16–18 . Genetic disease prevalence, and specific mutations causing autosomal recessive genetic diseases, are heritable, whereas reported race and ethnicity are imprecise social constructs that differ from ancestry and do not accurately predict genetic variants in individuals.…”

Section: Introductionmentioning

confidence: 99%

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Cystic fibrosis patients of minority race and ethnicity less likely eligible for CFTR modulators based on CFTR genotype

McGarry

McColley

2021

Self Cite

115

Background: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators are disease-modifying medications for cystic fibrosis (CF) and are shown to be efficacious for only specific CFTR mutations. CFTR mutation frequency varies by ancestry, which is different from but related to demographic racial and ethnic group. Eligibility for CFTR modulator therapy has not been previously reported by race and ethnicity.Methods: We conducted a cross-sectional study of patients in the 2018 CF Foundation Patient Registry. We analyzed the percentage of patients in each US Census defined racial and ethnic group eligible for CFTR modulators based on CFTR mutations approved by the US FDA and then based on both mutations and FDA approval by age.We compared lung function based on CFTR modulator eligibility and prescription.Findings: Based on CFTR mutations alone, 92.4% of non-Hispanic White patients, 69.7% of Black/African American patients, 75.6% of Hispanic patients, and 80.5% of other race patients eligible for CFTR modulators. For each CFTR modulator, Black/ African American patients were least likely to have eligible mutations, and non-Hispanic White patients were most likely. There was no difference in the disparity between racial and/or ethnic groups with the addition of current FDA approval by age. The lowest pulmonary function in the cohort was seen in non-Hispanic White, Black/African American, and Hispanic patients not eligible for CFTR modulators.Interpretation: Patients with CF from minority groups are less likely to be eligible for CFTR modulators. Because people with CF who are racial and ethnic minorities have increased disease severity and earlier mortality, this will further contribute to health disparities.

Improved detection of cystic fibrosis by the California Newborn Screening Program for all races and ethnicities

McGarry,

Sciortino,

Graham

et al. 2024

BackgroundNewborn screening (NBS) for cystic fibrosis (CF) is universal in the United States. Protocols vary but include an immunoreactive trypsinogen (IRT) level and CFTR variant panel. California CF NBS has a 3‐step screening: IRT level, variant panel, and CFTR sequencing if only one variant identified on panel.MethodsThis was a cohort study of infants with CF born in California (2007−2021) to examine racial and ethnic differences in having a false‐negative NBS result for CF and at which step the false‐negative occurred. We examined how different CFTR variant panels would improve detection of variants by race and ethnicity: original 39‐variant panel, current 75‐variant panel, and all 402 disease‐causing CFTR variants in the CFTR2 database.ResultsOf the 912 infants born in California with CF, 84 had a false‐negative result: 38 due to low IRT level and 46 with a high IRT value (but incomplete variant detection). Asian (OR 6.3) and Black infants (OR 2.5) were more likely to have a false‐negative screening result than non‐Hispanic white infants. The majority of false‐negative screening (but CF diagnosis) cases among American Indian/Native Alaskan and non‐Hispanic White infants were due to low IRT levels. The majority of Asian and Hispanic infants with false‐negative screening had no variants detected. Detection of two CFTR variants was improved with the 75‐variant panel in Black, Hispanic, and non‐Hispanic White infants and with the 402‐variant panel in Black, Hispanic, non‐Hispanic White, and other race infants.ConclusionsLarger CFTR panels in NBS improved the detection of CF in all races and ethnicities.