CFTR 5T VARIANT ANALYSIS
Congenital Bilateral Absence of Vas Deferens
DNA ANALYSIS

Cystic fibrosis (CF) is the most common autosomal recessive genetic disorder in the Caucasian population, and is caused by mutations in the CF transmembrane conductance regulator gene (CFTR). There is wide variability in clinical presentation. Most men with CF have congenital bilateral absence of the vas deferens (CBAVD) resulting in infertility. Otherwise healthy males may also have CBAVD, which is thought to be a CFTR-associated trait with incomplete penetrance. Approximately 40% of patients with CBAVD have been found to have the 5T variant on one of their CFTR gene copies. Approximately 70% of patients with CBAVD were found to have at least one CF mutation according to one study. The CFTR gene contains a polymorphic sequence of 5, 7, or 9 thymidine bases located at the splice branch/acceptor site of intron 8. The 5T variant has been shown to be the most common cause of CBAVD and is particularly associated with atypical CF expression, while the 7T and 9T variants are found on both normal and CF chromosomes. Of the CBAVD patients having one CF mutation, 63% also have the 5T variant. A combination of one CF mutation and the 5T variant on opposite copies of the CFTR gene is the most common cause of CBAVD. The variability in splicing efficiency and reduction in normal CFTR mRNA levels appears to be the molecular basis of atypical disease expression in patients having the 5T allele.

Reasons for Referral:

CBAVD patients who are either negative or heterozygous for a CF gene mutation. Note: CF gene mutation analysis should be done prior to or in conjunction with the 5T Variant analysis.
Individuals who are symptomatic for CF with one identified mutation.
Reproductive partners of CF carriers or CF patients

Testing Methodology:

Our laboratory utilizes an automated high-throughput system that incorporates DNA amplification (PCR), primer extension, and allele resolution by Matrix Assisted Laser Desorption Ionization-Time of Flight (MALDI-TOF) mass spectrometry to test for the polythymidine variant alleles at the branch/acceptor site in intron 8 of the CFTR gene. Allele sizes include: 5T, 7T, and 9T variants. Only the 5T variant has been associated with abnormal splicing and atypical CF expression, as well as CBAVD in otherwise healthy males.

Specimen Requirements:

Blood: EDTA (purple-top) tubes: Adults: 14 cc.
Requisition form must accompany specimen. Prior to any genetic testing, we recommend genetic counseling and request that the subject sign our consent form and submit it with the sample. To receive our forms, additional information, or kits, please contact our laboratory.

Turnaround Time:

3 weeks

CPT Codes and Prices:

83788, 83914x3, 83912, 83900, 83901, 83891

Shipping Information

Forms:

>> DNA Requisition

Test Code:

6017