Isolated CBAVD patients carry either a CF mutation ([DELTA]F508 in 16-83% of cases and R117H in 6-29% of cases) and/or a 5T variant in intron 8 (12-47% of patients), supporting the hypothesis that CBAVD represents a mild, primary genital form of CF (2-7).
We have developed a much faster, sensitive, single-step method to detect the IVS8 5T variant in CBAVD patients.
When R117H is in cis with 7T and another CF mutation is present on the other chromosome (in males), CBAVD
may result with or without late onset of mild lung disease (6,12).
01), suggesting that 5T might play a role in atypical sinopulmonary disease analogous to that reported for isolated CBAVD.
The appearance of genotypes previously described in mild CF and CBAVD among the ICP patients raised the possibility that other aspects of the greater CF phenotype might have gone unnoticed in these individuals.
Among the 19 CBAVD subjects investigated (of the 38 chromosomes analyzed), 8 (21%) carry the 5T variant, 19 (50%) the 7T variant, and 11 (29%) the 9T variant.
Typing of the poly-T tract in intron 8 of the CFTR gene in CBAVD subjects showed an increased proportion of the 5T variant in these subjects.
If the testing for this patient had stopped at this point, the interpretation would be that the results are consistent not only with a diagnosis of cystic fibrosis but also with CBAVD
2] Nonstandard abbreviations: CF, cystic fibrosis; CBAVD
, congenital bilateral absence of the vas deferens; ACMG, American College of Medical Genetics; ACOG, American College of Obstetricians and Gynecologists.
Our data confirm the high frequency of 5T-12TG in CBAVD
patients and do not preclude an effect in pancreatitis as well.
Whereas homozygosity for the [DELTA]F508 mutation will cause CF, double heterozygosity for the F508C mutation, in combination with either the [DELTA]F508 or [DELTA]I507 mutation, may cause CBAVD
While most patients with CBAVD
do not have clinical CF,[sup.