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MOLECULAR ANALYSIS:
CFTR Intron 8 Poly(T) Variant (CBAVD)
Cystic fibrosis (CF) is the most common autosomal recessive disorder in the Caucasian population. The disease is caused by mutations in the CF transmembrane conductance regulator gene (CFTR) located on chromosome 7. There is wide variability in clinical presentation among CF patients, probably due to the large number of disease causing mutations in the CFTR gene. More than 95% of men with CF are infertile due to congenital bilateral absence of the vas deferens (CBAVD). However, CBAVD may also be found among otherwise healthy males, accounting for 1 to 2 percent of cases of infertility in men. The frequency of CFTR gene mutations is increased among men with CBAVD, indicating that CBAVD is a CFTR associated disease with incomplete penetrance. Higher frequencies of CFTR gene mutations have also been found among men with congenital unilateral absence of the vas deferens (CUAVD) and among men with absence of the epididymis. Thus, cases of obstructive azoospermia caused by CFTR gene mutations may be considered CF cases with incomplete expression. The CFTR gene contains a polymorphic thymidine tract located at the branch/acceptor site of intron 8. The sequence may contain five, seven, or nine thymines. The 7T and 9T variants are associated with expected levels of normal CFTR protein. However, presence of the 5T variant results in inappropriate splicing of the mRNA and reduced levels of normal CFTR protein. Approximately 70% of men with CBAVD have at least one CF mutation. In CBAVD patients with one CF mutation, 63% also have the 5T variant. The most common cause of the CBAVD phenotype is a combination of one CF mutation and the 5T variant present on opposite copies (trans) of the CFTR gene.
DNA analysis for the CFTR intron 8 poly(T) variant may be ordered individually or in conjunction with cystic fibrosis testing. See Cystic Fibrosis for testing information.
- Males with a clinical diagnosis of obstructive azoospermia. These patients should have CFTR gene mutation testing and intron 8 poly(T) variant analysis.
Direct analysis: Our laboratory utilizes an automated high-throughput CF-OLA protocol involving polymerase chain reaction (PCR) amplification of specific regions of the CFTR gene followed by probing of the amplified regions using the Oligonucleotide Ligation Assay. This testing methodology detects the polymorphic thymidine tract at the branch/acceptor site of intron 8.
Blood: 5 cc collected in a purple top (EDTA) or yellow top (acid citrate dextrose) vacutainer tube. Do not centrifuge or freeze. Sample may be refrigerated or stored at room temperature.
10 - 12 days
83891, 83900, 83901, 83909, 83912, 83914
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