TY - JOUR
TI - Variation in a repeat sequence determines whether a common variant of
the cystic fibrosis transmembrane conductance regulator gene is
pathogenic or benign
AU - Groman, JD
AU - Hefferon, TW
AU - Casals, T
AU - Bassas, LS
AU - Estivill, X
AU - and Des Georges, M
AU - Guittard, C
AU - Koudova, M
AU - Fallin, MD and
AU - Nemeth, K
AU - Fekete, G
AU - Kadasi, L
AU - Friedman, K
AU - Schwarz, M and
AU - Bombieri, C
AU - Pignatti, PF
AU - Kanavakis, E
AU - Tzetis, M and
AU - Schwartz, M
AU - Novelli, G
AU - D'Apice, MR
AU - Sobczynska-Tomaszewska, A
AU - and Bal, J
AU - Stuhrmann, M
AU - Macek, M
AU - Claustres, M
AU - Cutting,
AU - GR
JO - American Journal of Human Genetics
PY - 2004
VL - 74
TODO - 1
SP - 176-179
PB - University of Chicago Press
SN - 0002-9297, 1537-6605
TODO - 10.1086/381001
TODO - null
TODO - An abbreviated tract of five thymidines (5T) in intron 8 of the cystic
fibrosis transmembrane conductance regulator ( CFTR) gene is found in
similar to 10% of individuals in the general population. When found in
trans with a severe CFTR mutation, 5T can result in male infertility,
nonclassic cystic fibrosis, or a normal phenotype. To test whether the
number of TG repeats adjacent to 5T influences disease penetrance, we
determined TG repeat number in 98 patients with male infertility due to
congenital absence of the vas deferens, 9 patients with nonclassic CF,
and 27 unaffected individuals ( fertile men). Each of the individuals in
this study had a severe CFTR mutation on one CFTR gene and 5T on the
other. Of the unaffected individuals, 78% ( 21 of 27) had 5T adjacent
to 11 TG repeats, compared with 9% ( 10 of 107) of affected
individuals. Conversely, 91% ( 97 of 107) of affected individuals had
12 or 13 TG repeats, versus only 22% ( 6 of 27) of unaffected
individuals (P < .00001). Those individuals with 5T adjacent to either
12 or 13 TG repeats were substantially more likely to exhibit an
abnormal phenotype than those with 5T adjacent to 11 TG repeats ( odds
ratio 34.0, 95% CI 11.1 - 103.7, P < .00001). Thus, determination of TG
repeat number will allow for more accurate prediction of benign versus
pathogenic 5T alleles.
ER -