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Test ID: CFPB    
Cystic Fibrosis Mutation Analysis, 106-Mutation Panel

Useful For Suggests clinical disorders or settings where the test may be helpful

Confirmation of a clinical diagnosis of cystic fibrosis

 

Risk refinement via carrier screening for individuals in the general population

 

Prenatal diagnosis or familial mutation testing when the familial mutations are included in the 106-mutation panel listed above (if familial mutations are not included in the 106-mutation panel, order CFTRK / CFTR Gene, Known Mutation)

 

Risk refinement via carrier screening for individuals with a family history when familial mutations are not available

 

Identification of patients who may respond to CFTR potentiator therapy

Genetics Test Information Provides information that may help with selection of the correct test or proper submission of the test request

106-Mutation panel includes the 23 mutations recommended by the American College of Medical Genetics (ACMG).

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Cystic fibrosis (CF), in the classic form, is a severe autosomal recessive disorder characterized by a varied degree of chronic obstructive lung disease and pancreatic enzyme insufficiency. The incidence of CF varies markedly among different populations, as does the mutation detection rate for the mutation screening assay. To date, over 1,500 mutations have been described within the CF gene, named cystic fibrosis transmembrane conductance regulator (CFTR). The most common mutation, deltaF508, accounts for approximately 67% of the mutations worldwide and approximately 70% to 75% in a North American Caucasian population. Most of the remaining mutations are rather rare, although some show a relatively higher prevalence in certain ethnic groups or in some atypical presentations of CF such as congenital bilateral absence of the vas deferens (CBAVD). Mutations detected by the assay performed in the Mayo Clinic Molecular Genetics Laboratory include the 23 mutations recommended by the American College of Medical Genetics as well as 83 other mutations.

 

Of note, CFTR potentiator therapies may improve clinical outcomes for patients with a clinical diagnosis of CF and at least 1 copy of the G551D mutation. 

 

These 106 mutations account for approximately 91% of CF chromosomes in a Northern European Caucasian population. Detection rates for several ethnic and racial groups are listed in the table below. Note that interpretation of test results and risk calculations are also dependent on clinical information and family history.

 

Racial or Ethnic Group

Carrier Frequency

Mutation Detection Rate*

 African American

1/65

81%

 Ashkenazi Jewish

1/25

97%

 Asian American (excluding individuals of Japanese ancestry)

1/90

54%

 Mixed European

1/25

82%

 Eastern European

1/25

77%

 French Canadian

1/25

91%

 Hispanic American

1/46

82%

 Northern European

1/25

91%

 Southern European

1/25

79%

                                                          

*Rates are for classical CF. Rates are lower for atypical forms of CF and for CBAVD.

 

CFTR mutations listed below are included in this panel.

Deletion exons 2-3

Exon 11: R553X

Intron 2: 296+2 T->A

Exon 11: A559T

Exon 3: E60X

Exon 11: R560T

Exon 3: R75X

Intron 11: 1811+1.6kb A->G

Exon 3: G85E

Intron 11: 1812-1 G->A

Exon 3: 394delTT

Intron 12: 1898+1 G->A

Intron 3: 405+1 G->A

Intron 12: 1898+1 G->T

Intron 3: 406-1 G->A

Intron 12: 1898+1 G->C

Exon 4: E92X

Intron 12: 1898+5 G->T

Exon 4: 444delA

Exon 12: P574H

Exon 4: 457TAT->G

Exon 13: 1949del84

Exon 4: R117H

Exon 13: 2043delG

Exon 4: R117C

Exon 13: 2055del9->A

Exon 4: Y122X

Exon 13: 2105del13ins5

Exon 4: 574delA

Exon 13: 2108delA

Intron 4: 621+1 G->T

Exon 13: 2143delT

Exon 5: 663delT

Exon 13: 2183AA->G

Exon 5: G178R

Exon 13: 2184delA

Intron 5: 711+1 G->T

Exon 13: 2184insA

Intron 5: 711+5 G->A

Exon 13: R709X

Intron 5: 712-1 G->T

Exon 13: K710X

Exon 6a: H199Y

Exon 13: 2307insA

Exon 6a: P205S

Exon 13: R764X

Exon 6a: L206W

Intron 14b: 2789+5 G->A

Exon 6a: 852del22

Exon 15: 2869insG

Exon 6b: 935delA

Exon 15: Q890X

Exon 6b: 936delTA

Intron 16: 3120+1 G->A

Exon 7: deltaF311

Exon 17a: 3171delC

Exon 7: 1078delT

Exon 17a: 3199del6

Exon 7: G330X

Exon 17b: R1066C

Exon 7: R334W

Exon 17b: W1089X

Exon 7: T338I

Exon 17b: Y1092X (C->G)

Exon 7: R347P

Exon 17b: Y1092X (C->A)

Exon 7: R347H

Exon 17b: M1101K

Exon 7: R352Q

Exon 17b: M1101R

Exon 7: Q359K

Exon 18: D1152H

Exon 7: T360K

Exon 19: R1158X

Exon 8: 1288insTA

Exon 19: R1162X

Exon 9: A455E

Exon 19: 3659delC

Exon 10: S466X (C->A)

Exon 19: 3667del4

Exon 10: S466X (C->G)

Exon 19: S1196X

Exon 10: G480C

Exon 19: W1204X

Exon 10: Q493X

Exon 19: 3791delC

Exon 10: deltaI507

Exon 19: Q1238X

Exon 10: deltaF508

Intron 19: 3849+10kb C->T

Exon 10: 1677delTA

Exon 20: 3876delA

Exon 10: C524X

Exon 20: S1251N

Intron 10: 1717-1 G->A

Exon 20: S1255X

Exon 11: G542X

Exon 20: 3905insT

Exon 11: S549N

Exon 20: W1282X

Exon 11: S549R

Exon 21: 4016insT

Exon 11: G551D

Exon 21: N1303K (C->A)

Exon 11:Q552X

Exon 21: N1303K (C->G)

 

See Cystic Fibrosis Molecular Diagnostic Testing Algorithm in Special Instructions for additional information.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation Provides information to assist in interpretation of the test results

An interpretive report will be provided.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This assay will not detect all of the mutations that cause cystic fibrosis. Therefore, the absence of a detectable mutation does not rule out the possibility that an individual is a carrier of or affected with this disease.

 

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.

 

Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.

 

In rare cases, DNA alterations of undetermined significance may be identified.

 

A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.

Clinical Reference Provides recommendations for further in-depth reading of a clinical nature

1. Quint A, Lerer I, Sagi M, Abeliovich D: Mutation spectrum in Jewish cystic fibrosis patients in Israel: implication to carrier screening. Am J Med Genet A 2005;136(3):246-248

2. Bobadilla JL, Macek M, Fine FP, Farrell PM: Cystic fibrosis: a worldwide analysis of CFTR mutations-correlation with incidence data and application to screening. Hum Mutat 2002;19(6):575-606

3. Sugarman EA, Rohlfs EM, Silverman LM, Alitto BA: CFTR mutation distribution among U.S. Hispanic and African American individuals: evaluation in cystic fibrosis patient and carrier screening populations. Genet Med 2004;6(5):392-399

4. Watson MS, Cutting GR, Desnick RJ, et al: Cystic fibrosis population carrier screening: 2004 revision of American College of Medical Genetics mutation panel. Genet Med 2004;6(5):387-391

5. Heim RA, Sugarman EA, Allitto BA: Improved detection of cystic fibrosis mutations in the heterozygous U.S. population using an expanded, pan-ethnic mutation panel. Genet Med 2001;3(3):168-176

6. Ramsey BW, Davies J, McElvaney NG, et al: A CFTR Potentiator in Patients with Cystic Fibrosis and the G551D Mutation. NEJM 2011 Nov 3:365(18):1663-1672

Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test