ABSTRACT
BACKGROUND: New York State (NYS) utilizes a three-tiered cystic fibrosis newborn screening (CFNBS) algorithm that includes cystic fibrosis transmembrane conductance regulator (CFTR) gene sequencing. Infants with >1 CFTR variant of potential clinical relevance, including variants of uncertain significance or varying clinical consequence are referred for diagnostic evaluation at NYS cystic fibrosis (CF) Specialty Care Centers (SCCs). AIMS: As part of ongoing quality improvement efforts, demographic, screening, diagnostic, and clinical data were evaluated for 289 CFNBS-positive infants identified in NYS between December 2017 and November 2020 who did not meet diagnostic criteria for CF and were classified as either: CFTR-related metabolic syndrome/CF screen positive, inconclusive diagnosis (CRMS/CFSPID) or CF carriers. RESULTS: Overall, 194/289 (67.1%) had CFTR phasing to confirm whether the infant's CFTR variants were in cis or in trans. Eighteen complex alleles were identified in cis; known haplotypes (p.R117H+5T, p.F508del+p.L467F, and p.R74W+p.D1270N) were the most common identified. Thirty-two infants (16.5%) with all variants in cis were reclassified as CF carriers rather than CRMS/CFSPID. Among 263 infants evaluated at an NYS SCC, 70.3% were reported as having received genetic counseling about their results by any provider, with 96/263 (36.5%) counseled by a certified genetic counselor. CONCLUSION: Given the particularly complex genetic interpretation of results generated by CFNBS algorithms including sequencing analysis, additional efforts are needed to ensure families of infants with a positive CFNBS result have CFTR phasing when needed to distinguish carriers from infants with CRMS/CFSPID, and access to genetic counseling to address implications of CFNBS results.
Subject(s)
Cystic Fibrosis Transmembrane Conductance Regulator , Cystic Fibrosis , Genetic Counseling , Genotype , Neonatal Screening , Parents , Humans , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , New York , Cystic Fibrosis/genetics , Infant, Newborn , Male , Female , Neonatal Screening/methods , Phenotype , Health Services Accessibility/statistics & numerical data , InfantSubject(s)
Congenital Bone Marrow Failure Syndromes , Humans , Infant, Newborn , New York , Follow-Up Studies , Female , MaleABSTRACT
The reference ranges for sweat [C1(-)] were reevaluated in 300 infants referred to our Center as carriers of at least 1 cystic fibrosis mutation identified through newborn screening. The recommended borderline range of 30 to 59 mmol/L failed to identify all individuals who were compound heterozygotes. Our data support using a borderline range of 24 to 59 mmol/L.