Mutations associated with cystic fibrosis
The present invention provides novel mutations identified in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that can be used for a more accurate diagnosis of cystic fibrosis (CF) and CF related disorders. Methods for testing a sample obtained from a subject to determine the presence of one or more mutations in the CFTR gene are provided wherein the presence of one or more mutations indicates that the subject has CF or a CF related disorder, or is a carrier of a CFTR mutation.
1. A method comprising:
detecting in a sample obtained from a human subject a 4089ins4 mutation of cystic fibrosis transmembrane conductance regulator (CFTR) gene using a plurality of labeled nucleic acid molecules, each comprising a label and a fragment of a CFTR gene nucleic acid sequence that specifically hybridizes to CFTR gene containing the 4089ins4 mutation but not to a wild-type CFTR gene, wherein the label comprises one of a radionucleotide, a fluorophore, a chemiluminescent agent, a microparticle, an enzyme, a colorimetric label, a magnetic label, a hapten, a molecular beacon, or an aptamer beacon.
2. The method of claim 1 , further comprising detecting in the sample one or more of a 269C>T, 2902G>T, 3814G>A, 502G>C, 1520G>T, 511-513 dup TTA, 978A>T, 843G>C, 829C>T, 4096-6C>T, 4375-7delT, 1586G>C, 875+4G>T, or 4005+3G>T mutation of CFTR gene using a plurality of labeled nucleic acid molecules, each comprising the label and a fragment of a CFTR gene nucleic acid sequence that specifically hybridizes to CFTR gene containing the one or more of the 269C>T, 2902G>T, 3814G>A, 502G>C, 1520G>T, 511-513 dup TTA, 978A>T, 843G>C, 829C>T, 4096-6C>T, 4375-7delT, 1586G>C, 875+4G>T, or 4005+3G>T mutation but not to the wild-type CFTR gene.
3. The method of claim 2 , wherein the one or more of the 269C>T, 2902G>T, 3814G>A, 502G>C, 1520G>T, 511-513 dup TTA, 978A>T, 843G>C, 829C>T, 4096-6C>T, 4375-7delT, 1586G>C, 875+4G>T, or 4005+3G>T mutation is detected as part of a CFTR mutation panel.
4. The method of claim 1 , further comprising detecting in the sample one or more of a 2711T>C, 3891G>C, 2524C>T or 2894G>A mutation of CFTR gene using a plurality of labeled nucleic acid molecules, each comprising the label and a fragment of a CFTR gene nucleic acid sequence that specifically hybridizes to CFTR gene containing the one or more of the 2711T>C, 3891G>C, 2524C>T or 2894G>A mutation but not to the wild-type CFTR gene.
5. The method of claim 4 , wherein the one or more of the 2711T>C, 3891G>C, 2524C>T or 2894G>A mutation is detected as part of a CFTR mutation panel.
6. The method of claim 1 , further comprising detecting in the sample one or more of a 405+10247C>T, 405+10255 del C, 1811+1643 G>T, 1812-13A>G, 2752-33insA, 3849+12192 G>A, 724G>A, 3899C>T, 3986C>T, 901G>A, 392T>C, 3463T>C, 1757G>A, 4025G>C, 4129G>T, 663T>G, 3200T>C, 4412T>C, 620A>C, 1738A>G, 3370A>C, 1129C>T, 2383C>T, 2761delTCT, 1106A>G or 622A>G mutation of CFTR gene using a plurality of labeled nucleic acid molecules, each comprising the label and a fragment of a CFTR gene nucleic acid sequence that specifically hybridizes to CFTR gene containing the one or more of the 405+10247C>T, 405+10255 del C, 1811+1643 G>T, 1812-13A>G, 2752-33insA, 3849+12192 G>A, 724G>A, 3899C>T, 3986C>T, 901G>A, 392T>C, 3463T>C, 1757G>A, 4025G>C, 4129G>T, 663T>G, 3200T>C, 4412T>C, 620A>C, 1738A>G, 3370A>C, 1129C>T, 2383C>T, 2761delTCT, 1106A>G or 622A>G mutation but not to the wild-type CFTR gene.
7. The method of claim 6 , wherein the one or more of the 405+10247C>T, 405+10255 del C, 1811+1643 G>T, 1812-13A>G, 2752-33insA, 3849+12192 G>A, 724G>A, 3899C>T, 3986C>T, 901G>A, 392T>C, 3463T>C, 1757G>A, 4025G>C, 4129G>T, 663T>G, 3200T>C, 4412T>C, 620A>C, 1738A>G, 3370A>C, 1129C>T, 2383C>T, 2761delTCT, 1106A>G or 622A>G mutation is detected as part of a CFTR mutation panel.
8. The method of claim 1 , further comprising detecting in the sample a 1824delA mutation of CFTR gene using a plurality of labeled nucleic acid molecules, each comprising the label and a fragment of a CFTR gene nucleic acid sequence that specifically hybridizes to CFTR gene containing the 1824delA mutation but not to the wild-type CFTR gene.
9. The method of claim 8 , wherein the 1824delA mutation is detected as part of a CFTR mutation panel.
10. The method of claim 1 , wherein the detecting step comprises performing hybridization.
11. The method of claim 10 , wherein the hybridization is performed with a microarray.
12. The method of claim 1 , wherein the detecting step comprises performing PCR amplification.
13. The method of claim 1 , wherein the detecting step comprises performing primer extension.
14. The method of claim 1 , wherein the 4089ins4 mutation is detected as part of a CFTR mutation panel.
15. The method of claim 14 , wherein the detecting step comprises performing hybridization.
16. The method of claim 15 , wherein the hybridization is performed with a microarray.
17. The method of claim 14 , wherein the detecting step comprises performing PCR amplification.
18. The method of claim 14 , wherein the detecting step comprises performing primer extension.
19. The method of claim 1 , further comprising detecting detecting in the sample one or more of a 2957delT, 4374+2T>C, 3064A>T, or 246C>G mutation using a plurality of labeled nucleic acid molecules, each comprising the label and a fragment of a CFTR gene nucleic acid sequence that specifically hybridizes to CFTR gene containing the one or more of a 2957delT, 4374+2T>C, 3064A>T, or 246C>G mutation but not to the wild-type CFTR gene.
20. The method of claim 19 , wherein the one or more of the 2957delT, 4374+2T>C, 3064A>T, or 246C>G mutation is detected as part of a CFTR mutation panel.