Identification of a splice site mutation (2789 + 5 G>A) associated with small amounts of normal CFTR mRNA and mild cystic fibrosis

W. Edward Highsmith; Lauranell H. Burch; Zhaoqing Zhou; John C. Olsen; Theresa V. Strong; Terry Smith; Kenneth J. Friedman; Lawrence M. Silverman; Richard C. Boucher; Francis S. Collins; Michael R. Knowles

doi:10.1002/(SICI)1098-1004(1997)9:4<332::AID-HUMU5>3.0.CO;2-7

Identification of a splice site mutation (2789 + 5 G>A) associated with small amounts of normal CFTR mRNA and mild cystic fibrosis

W. Edward Highsmith, Lauranell H. Burch, Zhaoqing Zhou, John C. Olsen, Theresa V. Strong, Terry Smith, Kenneth J. Friedman, Lawrence M. Silverman, Richard C. Boucher, Francis S. Collins, Michael R. Knowles

Laboratory Medicine and Pathology

Research output: Contribution to journal › Article › peer-review

68 Scopus citations

Abstract

A splicing mutation was identified at the +5 position of the splice donor site of exon 14b of CFTR in CF patients in a consanguineous family that is remarkable for unusually mild disease. Quantitative studies of nasal epithelial mRNA revealed that homozygotes for the spice site mutation produced approximately 4% of the normal amount of normally-spliced CFTR. We propose that this small amount of normally spliced mRNA is associated with synthesis of some normal CFTR protein, and accounts for the mild phenotype. Further characterization of epithelial function and clinical phenotype in patients bearing this form of mutation, termed a type V mutation, will be useful in determining the level of CFTR associated with amelioration of lung disease.

Original language	English (US)
Pages (from-to)	332-338
Number of pages	7
Journal	Human mutation
Volume	9
Issue number	4
DOIs	https://doi.org/10.1002/(SICI)1098-1004(1997)9:4<332::AID-HUMU5>3.0.CO;2-7
State	Published - 1997

Keywords

exon 14b
pancreatic sufficiency
quantitative CFTR mRNA

ASJC Scopus subject areas

Genetics
Genetics(clinical)

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10.1002/(SICI)1098-1004(1997)9:4<332::AID-HUMU5>3.0.CO;2-7

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Highsmith, W. E., Burch, L. H., Zhou, Z., Olsen, J. C., Strong, T. V., Smith, T., Friedman, K. J., Silverman, L. M., Boucher, R. C., Collins, F. S., & Knowles, M. R. (1997). Identification of a splice site mutation (2789 + 5 G>A) associated with small amounts of normal CFTR mRNA and mild cystic fibrosis. Human mutation, 9(4), 332-338. https://doi.org/10.1002/(SICI)1098-1004(1997)9:4<332::AID-HUMU5>3.0.CO;2-7

Highsmith, WE, Burch, LH, Zhou, Z, Olsen, JC, Strong, TV, Smith, T, Friedman, KJ, Silverman, LM, Boucher, RC, Collins, FS & Knowles, MR 1997, 'Identification of a splice site mutation (2789 + 5 G>A) associated with small amounts of normal CFTR mRNA and mild cystic fibrosis', Human mutation, vol. 9, no. 4, pp. 332-338. https://doi.org/10.1002/(SICI)1098-1004(1997)9:4<332::AID-HUMU5>3.0.CO;2-7

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title = "Identification of a splice site mutation (2789 + 5 G>A) associated with small amounts of normal CFTR mRNA and mild cystic fibrosis",

abstract = "A splicing mutation was identified at the +5 position of the splice donor site of exon 14b of CFTR in CF patients in a consanguineous family that is remarkable for unusually mild disease. Quantitative studies of nasal epithelial mRNA revealed that homozygotes for the spice site mutation produced approximately 4% of the normal amount of normally-spliced CFTR. We propose that this small amount of normally spliced mRNA is associated with synthesis of some normal CFTR protein, and accounts for the mild phenotype. Further characterization of epithelial function and clinical phenotype in patients bearing this form of mutation, termed a type V mutation, will be useful in determining the level of CFTR associated with amelioration of lung disease.",

keywords = "exon 14b, pancreatic sufficiency, quantitative CFTR mRNA",

author = "Highsmith, {W. Edward} and Burch, {Lauranell H.} and Zhaoqing Zhou and Olsen, {John C.} and Strong, {Theresa V.} and Terry Smith and Friedman, {Kenneth J.} and Silverman, {Lawrence M.} and Boucher, {Richard C.} and Collins, {Francis S.} and Knowles, {Michael R.}",

year = "1997",

doi = "10.1002/(SICI)1098-1004(1997)9:4<332::AID-HUMU5>3.0.CO;2-7",

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T1 - Identification of a splice site mutation (2789 + 5 G>A) associated with small amounts of normal CFTR mRNA and mild cystic fibrosis

AU - Highsmith, W. Edward

AU - Burch, Lauranell H.

AU - Zhou, Zhaoqing

AU - Olsen, John C.

AU - Strong, Theresa V.

AU - Smith, Terry

AU - Friedman, Kenneth J.

AU - Silverman, Lawrence M.

AU - Boucher, Richard C.

AU - Collins, Francis S.

AU - Knowles, Michael R.

PY - 1997

Y1 - 1997

N2 - A splicing mutation was identified at the +5 position of the splice donor site of exon 14b of CFTR in CF patients in a consanguineous family that is remarkable for unusually mild disease. Quantitative studies of nasal epithelial mRNA revealed that homozygotes for the spice site mutation produced approximately 4% of the normal amount of normally-spliced CFTR. We propose that this small amount of normally spliced mRNA is associated with synthesis of some normal CFTR protein, and accounts for the mild phenotype. Further characterization of epithelial function and clinical phenotype in patients bearing this form of mutation, termed a type V mutation, will be useful in determining the level of CFTR associated with amelioration of lung disease.

AB - A splicing mutation was identified at the +5 position of the splice donor site of exon 14b of CFTR in CF patients in a consanguineous family that is remarkable for unusually mild disease. Quantitative studies of nasal epithelial mRNA revealed that homozygotes for the spice site mutation produced approximately 4% of the normal amount of normally-spliced CFTR. We propose that this small amount of normally spliced mRNA is associated with synthesis of some normal CFTR protein, and accounts for the mild phenotype. Further characterization of epithelial function and clinical phenotype in patients bearing this form of mutation, termed a type V mutation, will be useful in determining the level of CFTR associated with amelioration of lung disease.

KW - exon 14b

KW - pancreatic sufficiency

KW - quantitative CFTR mRNA

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Identification of a splice site mutation (2789 + 5 G>A) associated with small amounts of normal CFTR mRNA and mild cystic fibrosis

Abstract

Keywords

ASJC Scopus subject areas

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