Cystic fibrosis screening using the College panel: Platform comparison and lessons learned from the first 20,000 samples

Purpose: To determine the accuracy of two commercially available kits for cystic fibrosis (CF) genotyping and determine allele frequencies for the ACMG/ACOG recommended mutations.Methods: A total of 1,040 consecutive analyses using Roche CF Gold Strips and the ABI CF Genotyper were performed. Subsequently we performed analyses of 20,103 samples.Results: Both kits accurately determined CF genotypes. The I148T mutation was found >100 times more frequently in carrier screening than in CF patients. Asymptomatic patients were identified who are compound heterozygotes for delta F508 and I148T. Four of 13 patients heterozygous for delta F508 and the IVS8-5T polymorphism had some symptoms of CF.Conclusion: Accurate and timely analysis can be performed for the ACMG CF panel. I148T is a low penetrance CF allele.

[1]  E. Girodon,et al.  Frequent Occurrence of the CFTR Intron 8 (TG)n 5T Allele in Men with Congenital Bilateral Absence of the Vas Deferens , 1995, European journal of human genetics : EJHG.

[2]  J. Haddow,et al.  Updated assessment of cystic fibrosis mutation frequencies in non-Hispanic Caucasians , 2002, Genetics in Medicine.

[3]  E. Buratti,et al.  Functional analysis of cis-acting elements regulating the alternative splicing of human CFTR exon 9. , 1999, Human molecular genetics.

[4]  Ronald G. Crystal,et al.  Genetic basis of variable exon 9 skipping in cystic fibrosis transmembrane conductance regulator mRNA , 1993, Nature Genetics.

[5]  M Claustres,et al.  Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens. , 1995, The New England journal of medicine.

[6]  B. Kerem,et al.  The molecular basis of partial penetrance of splicing mutations in cystic fibrosis. , 1997, American journal of human genetics.

[7]  R. Heim,et al.  Improved detection of cystic fibrosis mutations in the heterogeneous U.S. population using an expanded, pan-ethnic mutation panel , 2001, Genetics in medicine : official journal of the American College of Medical Genetics.

[8]  K. Klinger,et al.  Laboratory standards and guidelines for population-based cystic fibrosis carrier screening , 2001, Genetics in Medicine.

[9]  C. Férec,et al.  Complete and rapid scanning of the cystic fibrosis transmembrane conductance regulator (CFTR) gene by denaturing high-performance liquid chromatography (D-HPLC): major implications for genetic counselling , 2001, Human Genetics.