Cystic Fibrosis (including 508 FIRST, CF AMPLIFIED and CF 102)
Cystic Fibrosis (CF) affects approximately 30,000 children and adults in the US, and at least eight million Americans are asymptomatic carriers. Ambry Genetics is committed to CF caregivers and patients through diagnostic testing, research services, and community involvement.
PrintCystic Fibrosis (CF) affects approximately 30,000 children and adults in the US, and at least eight million Americans are asymptomatic carriers. Ambry Genetics is committed to CF caregivers and patients through diagnostic testing, research services, and community involvement.
The Ambry lab has analyzed the complete CF gene for more than 25,000 patients, providing the largest single-laboratory result database in the world from which to draw result interpretations.
The CF AMPLIFIED™ is the most comprehensive test available, detecting ~99% of mutations including gross deletions and duplications. The test begins with full gene sequence analysis which detects 97-98% of mutations. 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. It can be used for diagnosis in patients with a known or suspected diagnosis of CF, testing newborns who are found to have a single CF mutation on a newborn CF mutation screening test, and carrier testing for high-risk individuals and partners of CF mutation carriers.
The 508 FIRST™ test is for patients who have had no previous DNA testing. It provides a quick and inexpensive screen for deltaF508, the most common mutation. Positive results are reported in 3-5 days for diagnostic samples with homozygous deltaF508 and carrier screening samples with heterozygous deltaF508. Otherwise, testing automatically continues with CF AMPLIFIED™.
The Ambry CF 102™ Screening Panel is a panel of 102 CF mutations carefully selected to provide the highest overall mutation detection rate (91%) of any mutation panel currently on the market. It provides excellent sensitivity with a fast turnaround time and low cost. It is designed for patients who are known or suspected to have CF, for carrier screening for relatives of CF patients, and for carrier testing for known familial mutations.
Ambry also offers CF 33™, a 33-mutation screening panel, as well as a number of other flexible testing options to fit the needs of your patient.
Cystic Fibrosis (CF) is an autosomal recessive genetic disease affecting approximately 30,000 children and adults in the United States. CF has an incidence of approximately 1/3200 live births. The carrier frequency for non-Hispanic Caucasians is about one in 25, and lower in other ethnic groups. Two defective CF alleles cause the body to produce abnormally thick, sticky mucus that clogs the lungs and leads to life-threatening lung infections. People with CF have a variety of other symptoms including high sweat chloride levels, persistent coughing, wheezing or shortness of breath, and excessive appetite but poor weight gain. These thick secretions also obstruct the pancreas and prevent digestive enzymes from reaching the intestines to help break down and absorb food, contributing to pancreatitis. CF mutations may also lead to congenital bilateral absence of the vas deferens (CBAVD) and infertility. The severity of symptoms varies greatly between individuals diagnosed with CF due, in part, to the more than 1,500 different CF mutations described to date.
Genetic testing for CF is indicated for diagnosis in individuals with a known or suspected diagnosis of CF, for carrier testing in inviduals at increased risk based on ethnicity and/or family history, and for carrier testing in partners of individuals who carry a CF mutation.
Genomic deoxyribonucleic acid (gDNA) is isolated from the patients specimen using a standardized kit and quantified by agarose gel electrophoresis. Regions of gDNA for which testing is requested are selectively amplified through polymerase chain reaction (PCR). If only the deltaF508 mutation is to be analyzed first (508 FIRST) with a potential reflex to CF Screen 102 and full gene analysis, a simple method called Restriction Fragment Length Polymorphism (RFLP) is utilized. If CFTR full gene sequence analysis (Ambry Test: CF) is requested, a modified Temporal Temperature Gradient Electrophoresis (mTTGE) is utilized to scan for sequence variations. The exact nature of the sequence variation(s) detected by mTTGE are subsequently identified by automated sequencing using patient gDNA. If full gene sequence analysis plus reflexing to gross deletion/duplication (Ambry Test: CF AMPLIFIED) is requested, gene deletion/duplication analysis may, in addition, be performed using a Multiplex Ligation-dependent Probe Amplification (MLPA, MRC Holland).
508 FIRST detects only the deltaF508 mutation. For full gene analysis, sequence variations in the following CFTR promoter region, exons, and critical intronic regions that could contribute to CF are analyzed using the Ambry Test: CF: 983 bases of 5 untranslated region (UTR) and exons 1 to 24 (a total of 27 exons), plus at least 20 bases into the 5 and 3 ends of all the introns. CFTR poly T status, TG repeat, intron 19s 3849+10kbC>T mutation and intron 11s 1811+1634A>G mutation (aka 1811+1.6kbA>G) are also analyzed. Gross deletion/duplication analysis determines gene copy number for any of the 27 exons. All 23 ACOG and ACMG recommended mutations are analyzed using the Ambry Test: CF and Ambry Test: CF AMPLIFIED. Novel variants are always reported. Polymorphisms and the poly T status will be reported upon request.
The CF 102 Screening Panel targets detection of the following specific mutations in the CFTR gene: 1078delT (c.948delT), 1154insTC (c.1022_1023insTC), 1248+1G>A (c.1116+1G>A), 1288insTA (c.1153_1154insAT), 1471delA (c.1340delA), 1717-1G>A (c.1585-1G>A), 1898+1 G>A (c.1766+1G>A ), 1898+3A>G (c.1766+3A>G ), 1949del84 (c.1817_1900del84), 2055del9>A (c.1923_1931del9insA), 2143delT (c.2012delT), 2183AA>G (c.2051_2052delAAinsG), 2184delA (c.2052delA), 2184insA (c.2052insA), 2307insA (c.2175_2176insA), 2347delG (c.2215delG), 2585delT (c.2453delT), 2622+1G>A (c.2490+1G>A), 2789+2insA (c.2657+2_2657+3insA), 2789+5G>A (c.2657+5G>A), 3120+1G>A (c.2988+1G>A), 3120G>A (c.2988G>A), 3199del6 (c.3067_3072delATAGTG), 3272-26A>G (c.3140-26A>G), 3600G>A (c.3468G>A), 3659delC (c.3528delC), 3849+10kbC>T (c.3717+12191C>T), 3876delA (c.3744delA), 3905insT (c.3773_3774insT), 394delTT (c.262_263delTT), 4005+2T>C (c.3873+2T>C), 405+1G>A (c.273+1G>A), 406-1G>A (c.274-1G>A), 4209TGTT>AA (c.4077_4080delTGTTinsAA), 621+1G>T (c.489+1G>T), 663delT (c.531delT), 711+1G>T (c.579+1G>T), 935delA (c.803delA), p.A455E (c.1364C>A), p.D1152H (c.3454G>C), p.E116K (c.346G>A), p.E1371X (c.4111G>T), p.E384X (c.1150G>T), p.E585X (c.1753G>T), p.E60X (c.178G>T), p.E92X (c.274G>T), p.G1061R (c.3181G>C), p.G1244E (c.3731G>A), p.G178R (c.532G>A), p.G330X (c.988G>T), p.G480C (c.1438G>T), p.G542X (c.1624G>T), p.G551D (c.1652G>A), p.G551S (c.1651G>A), p.G85E (c.254G>A), EX2del, EX2_3del, deltaF508 (c.1521_1523delCTT), deltaI507 (c.1519_1521delATC), p.L1077P (c.3230T>C), p.L467P (c.1400T>C), p.M1101K (c.3302T>A), p.N1303K (c.3909C>G), p.P67L (c.200C>T), p.Q1042X (c.3124C>T), p.Q220X (c.658C>T), p.Q414X (c.1240C>T), p.Q493X (c.1477C>T), p.Q552X (c.1654C>T), p.Q98R (c.293A>G), p.Q98X (c.292C>T), p.R1066C (c.3196C>T), p.R1066H (c.3197G>A), p.R1070W (c.3208C>T), p.R1158X (c.3472C>T), p.R1162X (c.3484C>T), p.R117C (c.349C>T), p.R117H (c.350G>A), p.R334Q (c.1001G>A), p.R334W (c.1000C>T), p.R347H (c.1040G>A), p.R347P (c.1040G>C), p.R553X (c.1657C>T), p.R560T (c.1679G>C), p.R709X (c.2125C>T), p.R75X (c.223C>T), p.R764X (c.2290C>T), p.S1196X (c.3587C>G), p.S1251N (c.3752G>A), p.S466X (c.1397C>G), p.S489X (c.1466C>A), p.S549N (c.1646G>A), p.S912.
In the CF 33 Screening Panel, only the following 33 known disease-causing mutations on CFTR listed below are analyzed and reported; I507del,1717-1G>A, 1898+1G>A, 2184delA, 2789+5G>A, 3120+1G>A, 3659delC, 3849+10kbC>T, 3876delA, 394delTT, 621+1G>T, 711+1G>T, A455E, F508del, G542X, G551D, G85E, N1303K, Q493X, R1162X, R117H, R334W, R347P, R553X, R560T, S549N, W1282X, 2055del9>A, 406?1G>A, E60X, R1066C, S492F,2105-2117del13insAGAAA.
The following sites are used to search for previously described CF mutations and polymorphisms: Toronto Sick Childrens CF database, HGMD, and online search engines (i.e., PubMed).
508 First™ detects approximately 99% of CFTR mutations, including gross deletions and duplications, in patients of all ethnicities.
BLOOD: Collect 3-5 cc from adult or 2 cc minimum from child into EDTA purple-top tube (first choice) or ACD yellow-top tube (second choice). Store at room temperature or refrigerate. Ship at room temperature.
BLOOD SPOT: Minimum of one complete spot approximately 0.5 inch in diameter on S&S 903 collection paper or similar. Store in a clean plastic bag at room temperature. Ship at room temperature.
SALIVA: Collect 2 ml into Oragene™ DNA Self-Collection container. Store and ship at room temperature.
DNA: Send 20 μg in TE at 50-100 ng/μl. Store frozen and ship on ice or dry ice.
PRENATAL: Prenatal testing is available. Please call an Ambry Genetic Counselor to discuss your case.
| Test Code | Technique | CPT Codes |
|---|---|---|
| 1000 | CFTR Gene Sequence Analysis | 83891x1, 83894x2, 83898x50, 83903x29, 83904x1, 83909x1, 83912x1 |
| 1002 | 508 FIRST Reflex to CFTR Sequence Analysis and Deletion / Duplication | 83891x1, 83894x2, 83898x60, 83900x1, 83901x27, 83903x29, 83904x1, 83909x1, 83912x2 |
| 1004 | CFTR Deletion / Duplication Analysis | 83891x1, 83894x1, 83900x1, 83901x27, 83909x1, 83912x1 |
| 1006 | CFTR Sequence Analysis Reflex Option to Deletion / Duplication | 83891x1, 83894x2, 83898x60, 83900x1, 83901x27, 83903x29, 83904x1, 83909x1, 83912x2 |
| 1007 | CFTR Sequence Analysis Concurrent to Deletion / Duplication | 83891x1, 83894x2, 83898x60, 83900x1, 83901x27, 83903x29, 83904x1, 83909x1, 83912x2 |
| 1010 | CF TG Repeat (CFTR) | 83891x1, 83894x2, 83898x1, 83904x2, 83909x2, 83912x1 |
| 1012 | 508 ONLYTM (CFTR) | 83891x1, 83892x1, 83894x2, 83898x1, 83912x1 |
| 1018 | CFTR Screening Panel (CF102) | 83891x1, 83894x1, 83898x12, 83904x12, 83909x2, 83912x1 |
| 2000 | CFTR Screening Panel (CF33) | 83891x1, 83894x1, 83898x1, 83904x2, 83909x2, 83912x1 |
| Technique | Days |
|---|---|
| CFTR Gene Sequence Analysis | 14-28 |
| 508 FIRST Reflex to CFTR Sequence Analysis and Deletion / Duplication | 3-38 |
| CFTR Deletion / Duplication Analysis | 7-14 |
| CFTR Sequence Analysis Reflex Option to Deletion / Duplication | 21-35 |
| CFTR Sequence Analysis Concurrent to Deletion / Duplication | 14-28 |
| CF TG Repeat (CFTR) | 7-14 |
| 508 ONLYTM (CFTR) | 3-7 |
| CFTR Screening Panel (CF102) | 7-14 |
| CFTR Screening Panel (CF33) | 7-14 |