Cystic Fibrosis affects approximately 30,000 children and adults in the United States, according to the Cystic Fibrosis Foundation. The disease occurs in one out of every 3,500 children born in the U.S. Common symptoms include chronic cough, recurrent lung infections leading to diminished pulmonary function, pancreatic insufficiency, elevated sweat chlorides, and poor growth.

More than 10 million Americans are asymptomatic carriers of a defective cystic fibrosis transmembrane regulatory (CFTR) gene.
CF is inherited as an autosomal recessive disorder. When two carriers conceive, there is a 25% chance that the child will be a non-carrier, a 50% chance that the child will be a carrier, and a 25% chance that the child will have CF.

Ambry Genetics is committed to the CF community and has unprecedented knowledge and experience with cystic fibrosis disease-causing mutations. The Ambry lab has analyzed the complete CF gene for more than 10,000 patient samples, providing the largest single-laboratory cystic fibrosis test database in the world from which to draw result interpretations. To date, we have reported more than 700 different mutations in our patients. Our test is capable of detecting over 99% of the 1,500+ known mutations, as well as potential new mutations. We accept blood, bloodspots, saliva, and prenatal samples.

Results are reported directly to the referring physician or genetic counselor by phone, fax, and/or mail. Genetic Counselors are available for a thorough explanation of results and to address any questions or concerns about an abnormal report. The state of New York has approved Ambry’s CF testing services.

CF AMPLIFIED™ is the most comprehensive CF test available, detecting approximately 99% of mutations in patients of all ethnicities. The Ambry Test: CF AMPLIFIED begins with analysis of the full CFTR gene as well as surrounding critical introns by scanning and sequencing. If two mutations are detected in a diagnostic test, or one mutation in a carrier test, the testing is informative and the analysis is complete. If not, analysis automatically continues for gross deletions and duplications within the CFTR gene. Gross deletions and duplications are large rearrangements of the gene now understood to account for a small, but appreciable, percentage of CF mutations. Ambry Genetics was the first to introduce clinical testing for these rearrangements in 2005. Our experience and various publications show that deletions account for a significant fraction of cases in which typically affected CF patients were only diagnosed with one mutation in previous full gene sequence tests. Gross deletion and duplication analysis solves this diagnostic dilemma by finding the “missing mutation”.

Testing is done in steps to control costs; if deletion/duplication testing is not necessary, a discount is applied and the average turnaround time is reduced from 15-35 days to 14-28 days.

Further information is available in our linked materials at the end of this page.

508 FIRST provides a quick and inexpensive diagnosis of homozygous ΔF508 - the most common genotype occurring in up to 50% of classic CF patients. 508 FIRST is also an efficient option for carrier testing. Positive results are reported in 3-5 days. Testing is automatically reflexed to CF AMPLIFIED for diagnostic patients who do not have homozygous ΔF508 and carrier-test patients who are negative for ΔF508.

Further information is available in our linked materials at the end of this page.

Diagnosis of cystic fibrosis can be difficult due to variability in symptoms and a wide range in age of presentation. DNA testing has important role in confirming abnormalities of the CFTR protein. Testing for only select mutations is often ineffective in diagnostic testing because of the large number of known CF mutations, the small number of common mutations (only 7 occur with a frequency of >1%), and the fact that uncommon mutations can cause severe disease.

As described in our Gene Report 1, we reviewed a series of 877 samples from CF Centers that use Ambry Genetics’ full gene analysis for all new patients. Thirty-one percent of the mutations detected by the Ambry Test would have been missed by the ACMG 23-mutation panel. This equated to 34% of two-mutation positive patients that would not have been conclusively diagnosed if tested by the 23-mutation panel instead of the Ambry Test. Forty-one percent of these affected CF patients had homozygous deltaF508 mutations. These patients could have been diagnosed inexpensively in less than one week using Ambry Genetics’ 508 FIRST test, which is appropriate for all suspected CF patients who have not had previous DNA testing.

A definitive diagnosis provides a solid basis for proper therapy. When a comprehensive and reliable diagnosis is needed, the diagnostic test should be the Ambry Test.

Please see our new patient brochure Diagnostic Genetic Testing for Cystic Fibrosis.

Carrier status is most often determined by applying a screening panel of common mutations that includes 23 mutations specified by the American College of Medical Genetics. Detection rates of mutation panels vary by ethnicity and for the basic 23-mutation panel, they range from 88% down to 49% in the major American ethnic groups. Laboratories may test for additional mutations to increase the detection rates, but mutation panels do not achieve the Ambry Test: CF AMPLIFIED’s rate of approximately 99% in all ethnicities.

The table below shows background carrier rates, detection rates, and revised carrier risks for various ethnicities. The revised carrier risk is the chance, which exists after any CF genetic test, that a mutation went undetected. The CF AMPLIFIED test provides a significant reduction to the revised carrier risk.

Ethnicity	23-Mutation Panel Detection Rate	CF AMPLIFIED Detection Rate	Background Carrier Risk before Any Test	Revised Carrier Risk After 23-Mutation Panel	Revised Carrier Risk after CF AMPLIFIED
Non-Hispanic Caucasian	88%	99%	1/25	1/206	1/2401
Hispanic American	72%	99%	1/58	1/203	1/5701
African American	64%	99%	1/61	1/171	1/6001
Asian American	49%	99%	1/94	1/183	1/9301
Ashkenazi Jewish	94%	99%	1/24	1/384	1/2301

Ref: ACMG Technical Standards and Guidelines for CFTR Mutation Testing, 2006 Edition.
Calculations assume a negative test result and no family history of CF.

For general screening purposes, a small to moderate amount of uncertainty is acceptable to many patients. However, there are specific circumstances where a higher degree of confidence is desired. These include the following:

• One partner is known to be a CF carrier
• One partner is non-Caucasian
• Fetal ultrasound shows findings associated with CF
• Family history of CF
• Gamete donors

For these groups, comprehensive testing by the Ambry Test provides the greatest chance of mutation detection possible for the most informed diagnosis and patient care.

Further information is available in our new patient brochure Genetic Testing for Cystic Fibrosis Carrier Status .

For more information on Cystic Fibrosis Testing fill out our online form

Cystic Fibrosis Testing Options
    (Abobe PDF document)

    Gene Report Volume 1
A Comparison of Ambry Genetics’ Full Gene Sequence Analysis to    Common Mutation Testing in the Diagnosis of Cystic Fibrosis
    (Abobe PDF document)

    Gene Report Volume 2
Genetic Testing for the High-risk Cystic Fibrosis Carrier
    (Abobe PDF document)

    Patient Brochure
Diagnostic Genetic Testing for Cystic Fibrosis – Q & A for Patients
   and Families
    (Abobe PDF document)

    Patient Brochure
Genetic Testing for Cystic Fibrosis Carrier Status – Q & A for Patients    and Families
    (Abobe PDF document)

General Test Information
   The Ambry Test: Cystic Fibrosis
    (Abobe PDF document)

The following CPT Codes for The Ambry Test reflects Ambry Genetics’ interpretation of CPT coding requirements based on AMA guidelines:

Ambry Test®: 508 FIRST™* (CFTR)
83891, 83892, 83894, 83898, 83912

Ambry Test: CF Full Gene Analysis (CFTR)
83891, 83894, 83898, 83903, 83904, 83909, 83912

Ambry Test: CF AMPLIFIED™** (CFTR)
83891, 83894, 83898, 83903, 83904, 83900, 83901, 83909, 83912

Ambry Test: CF Del/Dup (CFTR)
83891, 83894, 83900, 83901, 83909, 83912

Ambry Test: TG Repeat
83891, 83894, 83898, 83904, 83909, 83912

*DeltaF508 detection only. If patient is not homozygous DeltaF508 for a diagnostic indication or a DeltaF508 heterozygote for a carrier screen, the sample is reflexed to CF AMPLIFIED. If del/dup testing is performed, the CF AMPLIFIED charges will apply and the 508 FIRST fee is waived. If the del/dup portion is not indicated, only the CF Full Gene Analysis charges will apply.
**Cystic Fibrosis Full Gene Sequence Analysis followed by the deletion/duplication test only if indicated.

CPT codes are provided only as a guide to assist you in billing. CPT coding is the sole responsibility of the billing party.

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Disclaimer:

This test was developed and its performance characteristic were determined by Ambry Genetics Corporation. The laboratory is regulated under the Clinical Laboratory Improvement Amendments 2003 as qualified to perform nonwaived testing. 508 FIRST™ analyzes only the Δ F508 mutation. The Ambry Test: CF analyzes the following types of mutations: nucleotide substitutions, small deletions, small insertions, and small indels, and the Ambry Test: CF AMPLIFIED analyzes, in addition, the gene’s gross deletion and duplication mutations. Neither method is intended to analyze the following types of mutations: gross insertions, gross rearrangements, deep intronic variations, and other unknown abnormalities. The pattern of mutation types varies with the gene tested and the Ambry Test detects a high but variable percentage of known and unknown mutants of the classes stated. A negative result from the analysis cannot rule out the possibility that the tested individual carries a rare unexamined mutation or mutation in the undetectable group. The Ambry Test: CF and CF AMPLIFIED are designed and validated to be capable of detecting about ~97-98% and ~99% of CF mutations, respectively (considering less than 1% being the other types of mutations). CF is a complex clinical disorder, which in the majority of cases is due to alterations in the CF gene generally detected by the Ambry Test: CF except as noted above. Mutations in other genes or the regions not tested by the Ambry Test: CF can also give rise to clinical conditions similar or identical to CF. Although molecular tests are highly accurate, rare diagnostic errors may occur. Possible diagnostic errors include sample mix-up, erroneous paternity identification, technical errors, and genotyping errors. Genotyping errors can result from trace contamination of PCR reactions, from maternal cell contamination in fetal samples, from rare genetic variants, which interfere with analysis, or from other sources. This report does not represent medical advice. Any questions, suggestions, or concerns regarding interpretation of results should be forwarded to a genetic counselor, medical geneticist, or physician skilled in interpretation of the relevant medical literature. References are available upon request. Conclusion of Cystic Fibrosis Testing information.