Genotype-phenotype correlation and frequency of the 3199del6 cystic fibrosis mutation among I148T carriers: Results from a collaborative study

K. G. Monaghan, W Edward Jr. Highsmith, J. Amos, V. M. Pratt, B. Roa, M. Friez, L. L. Pike-Buchanan, I. M. Buyse, J. B. Redman, C. M. Strom, A. L. Young, W. Sun

Research output: Contribution to journalArticle

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Abstract

Purpose: We expect that the mutation panel currently recommended for preconception/prenatal CF carrier screening will be modified as new information is learned regarding the phenotype associated with specific mutations and allele frequencies in various populations. One such example is the I148T mutation, originally described as a severe CF mutation. After implementation of CF population-based carrier screening, we learned that I148T exists as a complex allele with 3199del6 in patients with clinical CF, whereas asymptomatic compound heterozygotes for I148T and a second severe CF mutation were negative for 3199del6. Methods: We performed reflex testing for 3199del6 on 663 unrelated specimens, including I148T heterozygotes, compound heterozygotes, and a homozygous individual. Results: Less than 1% of I148T carriers were also positive for 3199del6. Excluding subjects tested because of a suspected or known CF diagnosis or positive family history, 0.6% of I148T-positive individuals were also positive for 3199del6. We identified 1 I148T homozygote and 6 unrelated compound heterozygous individuals with I148T and a second CF variant (2 of whom also carried 3199del6). In addition, one fetus with echogenic bowel and one infertile male were heterozygous for I148T (3199del6 negative). Conclusions: Reflex testing for 3199del6 should be considered whenever I148T is identified. Reflex testing is of particular importance for any symptomatic patient or whenever one member of a couple carries a deleterious CF mutation and the other member is an I148T heterozygote. Further population data are required to determine if I148T, in the absence of 3199del6, is associated with mild or atypical CF or male infertility.

Original languageEnglish (US)
Pages (from-to)421-425
Number of pages5
JournalGenetics in Medicine
Volume6
Issue number5
DOIs
StatePublished - Sep 2004

Fingerprint

Genetic Association Studies
Cystic Fibrosis
Heterozygote
Mutation
Reflex
Echogenic Bowel
Population
Male Infertility
Homozygote
Mutation Rate
Gene Frequency
Fetus
Alleles
Phenotype

Keywords

  • 3199del6
  • Cystic fibrosis
  • I148T
  • Mutation analysis

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Genotype-phenotype correlation and frequency of the 3199del6 cystic fibrosis mutation among I148T carriers : Results from a collaborative study. / Monaghan, K. G.; Highsmith, W Edward Jr.; Amos, J.; Pratt, V. M.; Roa, B.; Friez, M.; Pike-Buchanan, L. L.; Buyse, I. M.; Redman, J. B.; Strom, C. M.; Young, A. L.; Sun, W.

In: Genetics in Medicine, Vol. 6, No. 5, 09.2004, p. 421-425.

Research output: Contribution to journalArticle

Monaghan, KG, Highsmith, WEJ, Amos, J, Pratt, VM, Roa, B, Friez, M, Pike-Buchanan, LL, Buyse, IM, Redman, JB, Strom, CM, Young, AL & Sun, W 2004, 'Genotype-phenotype correlation and frequency of the 3199del6 cystic fibrosis mutation among I148T carriers: Results from a collaborative study', Genetics in Medicine, vol. 6, no. 5, pp. 421-425. https://doi.org/10.1097/01.GIM.0000139507.20179.3A
Monaghan, K. G. ; Highsmith, W Edward Jr. ; Amos, J. ; Pratt, V. M. ; Roa, B. ; Friez, M. ; Pike-Buchanan, L. L. ; Buyse, I. M. ; Redman, J. B. ; Strom, C. M. ; Young, A. L. ; Sun, W. / Genotype-phenotype correlation and frequency of the 3199del6 cystic fibrosis mutation among I148T carriers : Results from a collaborative study. In: Genetics in Medicine. 2004 ; Vol. 6, No. 5. pp. 421-425.
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abstract = "Purpose: We expect that the mutation panel currently recommended for preconception/prenatal CF carrier screening will be modified as new information is learned regarding the phenotype associated with specific mutations and allele frequencies in various populations. One such example is the I148T mutation, originally described as a severe CF mutation. After implementation of CF population-based carrier screening, we learned that I148T exists as a complex allele with 3199del6 in patients with clinical CF, whereas asymptomatic compound heterozygotes for I148T and a second severe CF mutation were negative for 3199del6. Methods: We performed reflex testing for 3199del6 on 663 unrelated specimens, including I148T heterozygotes, compound heterozygotes, and a homozygous individual. Results: Less than 1{\%} of I148T carriers were also positive for 3199del6. Excluding subjects tested because of a suspected or known CF diagnosis or positive family history, 0.6{\%} of I148T-positive individuals were also positive for 3199del6. We identified 1 I148T homozygote and 6 unrelated compound heterozygous individuals with I148T and a second CF variant (2 of whom also carried 3199del6). In addition, one fetus with echogenic bowel and one infertile male were heterozygous for I148T (3199del6 negative). Conclusions: Reflex testing for 3199del6 should be considered whenever I148T is identified. Reflex testing is of particular importance for any symptomatic patient or whenever one member of a couple carries a deleterious CF mutation and the other member is an I148T heterozygote. Further population data are required to determine if I148T, in the absence of 3199del6, is associated with mild or atypical CF or male infertility.",
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T1 - Genotype-phenotype correlation and frequency of the 3199del6 cystic fibrosis mutation among I148T carriers

T2 - Results from a collaborative study

AU - Monaghan, K. G.

AU - Highsmith, W Edward Jr.

AU - Amos, J.

AU - Pratt, V. M.

AU - Roa, B.

AU - Friez, M.

AU - Pike-Buchanan, L. L.

AU - Buyse, I. M.

AU - Redman, J. B.

AU - Strom, C. M.

AU - Young, A. L.

AU - Sun, W.

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N2 - Purpose: We expect that the mutation panel currently recommended for preconception/prenatal CF carrier screening will be modified as new information is learned regarding the phenotype associated with specific mutations and allele frequencies in various populations. One such example is the I148T mutation, originally described as a severe CF mutation. After implementation of CF population-based carrier screening, we learned that I148T exists as a complex allele with 3199del6 in patients with clinical CF, whereas asymptomatic compound heterozygotes for I148T and a second severe CF mutation were negative for 3199del6. Methods: We performed reflex testing for 3199del6 on 663 unrelated specimens, including I148T heterozygotes, compound heterozygotes, and a homozygous individual. Results: Less than 1% of I148T carriers were also positive for 3199del6. Excluding subjects tested because of a suspected or known CF diagnosis or positive family history, 0.6% of I148T-positive individuals were also positive for 3199del6. We identified 1 I148T homozygote and 6 unrelated compound heterozygous individuals with I148T and a second CF variant (2 of whom also carried 3199del6). In addition, one fetus with echogenic bowel and one infertile male were heterozygous for I148T (3199del6 negative). Conclusions: Reflex testing for 3199del6 should be considered whenever I148T is identified. Reflex testing is of particular importance for any symptomatic patient or whenever one member of a couple carries a deleterious CF mutation and the other member is an I148T heterozygote. Further population data are required to determine if I148T, in the absence of 3199del6, is associated with mild or atypical CF or male infertility.

AB - Purpose: We expect that the mutation panel currently recommended for preconception/prenatal CF carrier screening will be modified as new information is learned regarding the phenotype associated with specific mutations and allele frequencies in various populations. One such example is the I148T mutation, originally described as a severe CF mutation. After implementation of CF population-based carrier screening, we learned that I148T exists as a complex allele with 3199del6 in patients with clinical CF, whereas asymptomatic compound heterozygotes for I148T and a second severe CF mutation were negative for 3199del6. Methods: We performed reflex testing for 3199del6 on 663 unrelated specimens, including I148T heterozygotes, compound heterozygotes, and a homozygous individual. Results: Less than 1% of I148T carriers were also positive for 3199del6. Excluding subjects tested because of a suspected or known CF diagnosis or positive family history, 0.6% of I148T-positive individuals were also positive for 3199del6. We identified 1 I148T homozygote and 6 unrelated compound heterozygous individuals with I148T and a second CF variant (2 of whom also carried 3199del6). In addition, one fetus with echogenic bowel and one infertile male were heterozygous for I148T (3199del6 negative). Conclusions: Reflex testing for 3199del6 should be considered whenever I148T is identified. Reflex testing is of particular importance for any symptomatic patient or whenever one member of a couple carries a deleterious CF mutation and the other member is an I148T heterozygote. Further population data are required to determine if I148T, in the absence of 3199del6, is associated with mild or atypical CF or male infertility.

KW - 3199del6

KW - Cystic fibrosis

KW - I148T

KW - Mutation analysis

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