Abstract
An abbreviated tract of five thymidines (5T) in intron 8 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene is found in ∼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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 176-179 |
| Number of pages | 4 |
| Journal | American Journal of Human Genetics |
| Volume | 74 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2004 |
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ASJC Scopus subject areas
- Genetics
Cite this
Variation in a Repeat Sequence Determines Whether a Common Variant of the Cystic Fibrosis Transmembrane Conductance Regulator Gene Is Pathogenic or Benign. / Groman, Joshua D.; Hefferon, Timothy W.; Casals, Teresa; Bassas, Lluís; Estivill, Xavier; Des Georges, Marie; Guittard, Caroline; Koudova, Monika; Fallin, Daniele Daniele; Nemeth, Krisztina; Fekete, Gyorgy; Kadasi, Ludovit; Friedman, Ken; Schwarz, Martin; Bombieri, Cristina; Pignatti, Pier Franco; Kanavakis, Emmanuel; Tzetis, Maria; Schwartz, Marianne; Novelli, Giuseppe; D'Apice, Maria Rosaria; Sobczynska-Tomaszewska, Agnieszka; Bal, Jerzy; Stuhrmann, Manfred; Macek, Milan; Claustres, Mireille; Cutting, Garry R.
In: American Journal of Human Genetics, Vol. 74, No. 1, 01.2004, p. 176-179.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Variation in a Repeat Sequence Determines Whether a Common Variant of the Cystic Fibrosis Transmembrane Conductance Regulator Gene Is Pathogenic or Benign
AU - Groman, Joshua D.
AU - Hefferon, Timothy W.
AU - Casals, Teresa
AU - Bassas, Lluís
AU - Estivill, Xavier
AU - Des Georges, Marie
AU - Guittard, Caroline
AU - Koudova, Monika
AU - Fallin, Daniele Daniele
AU - Nemeth, Krisztina
AU - Fekete, Gyorgy
AU - Kadasi, Ludovit
AU - Friedman, Ken
AU - Schwarz, Martin
AU - Bombieri, Cristina
AU - Pignatti, Pier Franco
AU - Kanavakis, Emmanuel
AU - Tzetis, Maria
AU - Schwartz, Marianne
AU - Novelli, Giuseppe
AU - D'Apice, Maria Rosaria
AU - Sobczynska-Tomaszewska, Agnieszka
AU - Bal, Jerzy
AU - Stuhrmann, Manfred
AU - Macek, Milan
AU - Claustres, Mireille
AU - Cutting, Garry R
PY - 2004/1
Y1 - 2004/1
N2 - An abbreviated tract of five thymidines (5T) in intron 8 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene is found in ∼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.
AB - An abbreviated tract of five thymidines (5T) in intron 8 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene is found in ∼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.
UR - http://www.scopus.com/inward/record.url?scp=9144235448&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=9144235448&partnerID=8YFLogxK
U2 - 10.1086/381001
DO - 10.1086/381001
M3 - Article
C2 - 14685937
AN - SCOPUS:9144235448
VL - 74
SP - 176
EP - 179
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 1
ER -