Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (885 page)

   
Normal values:
negative or no mutations are found.

   Use

   Confirmatory diagnostic testing

   Carrier testing (for the identification of heterozygotes)

   Prenatal diagnosis

   Available tests can be grouped as

   Targeted mutation analysis tests.

   23-mutation panel recommended by the ACMG in 2004.

   Panels testing for more than 23 mutations.

   Reflex testing for the poly T variant (5T/7T/9T), a string of thymidine bases located in intron 8, is recommended for individuals having the
R117H
mutation or an adult male patient who is being evaluated for congenital absence of the vas deferens (CAVD). The 5T variant is thought to decrease the efficiency of intron 8 splicing.

   Sequence analysis: Analysis of the entire coding region, promoter exon– intron boundaries, and specific intronic regions—testing to identify rare mutant alleles.

   Deletion analysis: By MLPA (multiplex ligation–dependent probe amplification) or other molecular method.

   Next-generation sequencing represents an integration of carrier screening and diagnostic testing in one lab test. Differentiation between CF screening and CF diagnostic testing occurs during the software analysis. CF screening software allows viewing of sequencing results according to a predetermined panel of clinically relevant CFTR mutations. CF diagnostic software allows one to see all variants found within the CFTR gene. The complexity of the interpretation of the results is much higher for the diagnostic test than for carrier screening test.