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Screening and Diagnosis

Zvereff VV, Faruki H, Edwards M et al.

Laboratory Corporation of America, Research Triangle Park, NC, USA.

 Genet Med 2013 Dec 19; Epub ahead of print.

Aleksandra Norek’s review: Although cystic fibrosis (CF) is most prevalent in white individuals (one in 2500), it is a pan-ethnic disease in North America and is found in African-American (one in 15000), Hispanic-American (one in 13500), and Asian-American (one in 35000) individuals. In 2001, the American College of Medical Genetics and Genomics (ACMG) and the American College of Obstetricians and Gynecologists (ACOG) recommended a 25-mutation panel for CF carrier screening; this was later refined to a panel with 23 mutations (Genet Med 2004;6:387–91). The selection of CF transmembrane conductance regulator (CFTR) gene variants in the panel was based on pathogenicity and an allele frequency of ≥0.1% in the general CF population in the US. The panel was originally designed for the white and Ashkenazi Jewish populations and excluded mutations important in other ethnic groups that constitute significant components of the American mosaic. A number of studies have identified apparent race-specific alleles in affected individuals. Those race-specific alleles with the highest frequency have been recommended as additions to the current 23-mutation panel in order to increase CF carrier detection rates in ethnic populations in the US.

The purpose of the current study was to evaluate the mutation frequency distribution observed in a CF carrier population using a 32-mutation panel by way of an oligonucleotide ligation assay (Celera Diagnostics, Alameda, CA, USA) versus a 69-mutation panel by way of the Universal Array Platform (Luminex, Toronto, ON, Canada). In addition, the race-specific detection rates provided by both panels were determined, and the performance of extended CFTR mutation panels in large-scale, population-based CF carrier screening was assessed. DNA samples from 1711138 individuals were referred for CF screening using the 32-mutation panel (n=1601308) or the 69-mutation panel (n=109830). These panels incorporated all the variants from the ACMG/ACOG panel together with additional pathogenic variants present in white, Hispanic, and African-American populations with a frequency that matched or exceeded the ACMG/ACOG 0.1% prevalence threshold.

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