# US 10,865,450 B2 · Mutations associated with cystic fibrosis

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 10,865,450 B2
- Document ID: US10865450B2
- Status: Granted
- Kind: B2
- Application number: 16/253,860
- Filed: 2019-01-22
- Published: 2019-12-05
- Granted: 2020-12-15
- Earliest claimed: 2010-03-22
- Assignees: Laboratory Corporation of America Holdings
- Applicants: Laboratory Corporation of America Holdings
- Inventors: Elizabeth Rohlfs; Deborah Alexa Sirko-Osadsa; Lynne Rosenblum; Narasimhan Nagan; Zhaoqing Zhou; Ruth Heim
- Web page: https://patentgrep.com/patent/US10865450B2

## CPC

- C12Q 1/6883: for diseases caused by alterations of genetic material
- C12Q 1/6816: characterised by the detection means (C12Q1/6804 takes precedence)
- G01N 33/6872: {Intracellular protein regulatory factors and their receptors, e.g. including ion channels}
- C12Q 2600/112: Disease subtyping, staging or classification
- C12Q 2600/156: Polymorphic or mutational markers
- C12Q 2600/16: Primer sets for multiplex assays
- G01N 2800/382: Cystic fibrosis
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

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.

## Claims

### Claim 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.

### Claim 2 (depends on 1)

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.

### Claim 3 (depends on 2)

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.

### Claim 4 (depends on 1)

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.

### Claim 5 (depends on 4)

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.

### Claim 6 (depends on 1)

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.

### Claim 7 (depends on 6)

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.

### Claim 8 (depends on 1)

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.

### Claim 9 (depends on 8)

The method of claim 8, wherein the 1824delA mutation is detected as part of a CFTR mutation panel.

### Claim 10 (depends on 1)

The method of claim 1, wherein the detecting step comprises performing hybridization.

### Claim 11 (depends on 10)

The method of claim 10, wherein the hybridization is performed with a microarray.

### Claim 12 (depends on 1)

The method of claim 1, wherein the detecting step comprises performing PCR amplification.

### Claim 13 (depends on 1)

The method of claim 1, wherein the detecting step comprises performing primer extension.

### Claim 14 (depends on 1)

The method of claim 1, wherein the 4089ins4 mutation is detected as part of a CFTR mutation panel.

### Claim 15 (depends on 14)

The method of claim 14, wherein the detecting step comprises performing hybridization.

### Claim 16 (depends on 15)

The method of claim 15, wherein the hybridization is performed with a microarray.

### Claim 17 (depends on 14)

The method of claim 14, wherein the detecting step comprises performing PCR amplification.

### Claim 18 (depends on 14)

The method of claim 14, wherein the detecting step comprises performing primer extension.

### Claim 19 (depends on 1)

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.

### Claim 20 (depends on 19)

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.