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

Abstract

Background In cystic fibrosis (CF), the spectrum and frequency of CFTR variants differ by geography and race/ethnicity. CFTR variants in White patients are well‐described compared with Latino patients. No studies of CFTR variants have been done in patients with CF in the Dominican Republic or Puerto Rico. Methods CFTR was sequenced in 61 Dominican Republican patients and 21 Puerto Rican patients with CF and greater than ​​​​60 mmol/L sweat chloride. The spectrum of CFTR variants was identified and the proportion of patients with 0, 1, or 2 CFTR variants identified was determined. The functional effects of identified CFTR variants were investigated using clinical annotation databases and computational prediction tools. Results Our study found 10% of Dominican patients had two CFTR variants identified compared with 81% of Puerto Rican patients. No CFTR variants were identified in 69% of Dominican patients and 10% of Puerto Rican patients. In Dominican patients, there were 19 identified CFTR variants, accounting for 25 out of 122 disease alleles (20%). In Puerto Rican patients, there were 16 identified CFTR variants, accounting for 36 out of 42 disease alleles (86%) in Puerto Rican patients. Thirty CFTR variants were identified overall. The most frequent variants for Dominican patients were p.Phe508del and p.Ala559Thr and for Puerto Rican patients were p.Phe508del, p.Arg1066Cys, p.Arg334Trp, and p.I507del. Conclusions In this first description of the CFTR variants in patients with CF from the Dominican Republic and Puerto Rico, there was a low detection rate of two CFTR variants after full sequencing with the majority of patients from the Dominican Republic without identified variants.

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

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

“…CFTR variant type and frequency vary across races and ethnicities dependent on ancestry admixture and migration patterns, but race and ethnicity are not reliable proxies for ancestry. For example, Hispanic populations have different CFTR variant type and frequency, even when closely geographically located 35 . Furthermore, CFTR variants are not well mapped in the African diaspora, which has the most genetic heterogeneity globally.…”

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

“…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.…”

“…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.…”

“…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.…”