Cystic Fibrosis Targeted Mutation Analysis
Cystic fibrosis (CF) is one of the most common autosomal recessive disorders in the Caucasian population, with a carrier frequency of approximately 1 in 25. This condition affects epithelia of the respiratory tract, exocrine pancreas, intestine, male genital tract, hepatobiliary system, and exocrine sweat glands, resulting in complex multisystem disease. Disease expression is variable and can range from mild pulmonary and pancreatic involvement to severe progressive obstructive lung disease with pancreatic insufficiency and early mortality. Males with CF are also typically infertile. CF occurs in approximately 1 in 3,200 Caucasian individuals, but has been reported across all races, ethnicities, and ancestries.
CFTR (cystic fibrosis transmembrane conductance regulator) is the only gene known to be associated with cystic fibrosis. To date, there have been more than 700 DNA variants identified in the CFTR gene. The frequency of each variant varies among different populations, both geographically and ethnically. Genetics Center’s targeted CF panel detects 119 different known disease-causing CFTR variants including the 100 variants recommended by the American College of Medical Genetics and Genomics (ACMG). For a more comprehensive approach, CFTR full gene sequence analysis is also available through Genetics Center's Molecular Laboratory.
Reasons for Referral
- Diagnostic clarification for individuals with elevated sweat chloride concentrations
- Individuals with chronic lung disease, failure to thrive, or other evidence of cystic fibrosis.
- Carrier screening for prenatal patients or patients who are considering pregnancy.
- Carrier screening for individuals with a family history of cystic fibrosis.
Testing Methods
DNA is chemically isolated and the areas of interest are amplified by polymerase chain reaction (PCR) and then sequenced using Next Generation Sequencing. All reported variants are confirmed by Sanger sequencing. 119 CFTR variants and one normal variant are detected by this assay: c.4C>T (p.Gln2*), c.178G>T (p.Glu60*), c.200C>T (p.Pro67Leu), c.223C>T (p.Arg75*), c.254G>A (p.Gly85Glu), c.262_263delTT (p.Leu88Ilefs*22), c.271G>A (p.Gly91Arg), c.274-1G>A, c.292C>T (p.Gln98*), c.293A>G (p.Gln98Arg), c.313delA (p.Ile105Serfs*2), c.328G>C (p.Asp110His), c.349C>T (p.Arg117Cys), c.350G>A (p.Arg117His), c.366T>A (p.Tyr122*), c.489+1G>T, c.571T>G (p.Phe191Val), c.579+1G>T, c.579+3A>G, c.617T>G (p.Leu206Trp), c.653T>A (p.Leu218*), c.695T>A (p.Val232Asp), c.803delA (p.Asn268Ilefs*17), c.868C>T (p.Gln290*), c.948delT (p.Phe316Leufs*12), c.988G>T (p.Gly330*), c.1000C>T (p.Arg334Trp), c.1013C>T (p.Thr338Ile), c.1021_1022dupTC (p.Phe342Hisfs*28), c.1029delC (p.Cys343*), c.1040G>A (p.Arg347His), c.1040G>C (p.Arg347Pro), c.1055G>A (p.Arg352Gln), c.1155_1156dupTA (p.Asn386Ilefs*3), c.1327_1330dupGATA (p.Ile444Argfs*3), c.1364C>A (p.Ala455Glu), c.1367T>C (p.Val456Ala), c.1373delG (p.Gly458Aspfs*11), c.1393-1G>A, c.1397C>G (p.Ser466*), c.1397C>A (p.Ser466*), c.1400T>C (p.Leu467Pro), c.1477C>T (p.Gln493*), c.1519_1521delATC (p.Ile507del), c.1521_1523delCTT (p.Phe508del), c.1523T>G (p.Phe508Cys), c.1558G>T (p.Val520Phe), c.1572C>A (p.Cys524*), c.1584+1G>A, c.1585-1G>A, c.1624G>T (p.Gly542*), c.1645A>C (p.Ser549Arg), c.1646G>A (p.Ser549Asn), c.1647T>A (p.Ser549Arg), c.1647T>G (p.Ser549Arg), c.1651G>A (p.Gly551Ser), c.1652G>A (p.Gly551Asp), c.1657C>T (p.Arg553*), c.1673T>C (p.Leu558Ser), c.1675G>A (p.Ala559Thr), c.1679G>C (p.Arg560Thr), c.1679+1G>A, c.1680-886A>G, c.1680A>C (p.Arg560Ser), c.1680A>T (p.Arg560Ser), c.1682C>A (p.Ala561Glu), c.1692delA (p.Asp565Metfs*7), c.1705T>G (p.Tyr569Asp), c.1753G>T (p.Glu585*), c.1766+1G>A, c.1766+1G>C, c.1766+5G>T, c.1837G>A (p.Ala613Thr), c.1882G>A (p.Gly628Arg), c.1882G>C (p.Gly628Arg), c.2052delA (p.Lys684Asnfs*38), c.2052dupA (p.Gln685Thrfs*4), c.2051_2052delAAinsG (p.Lys684Serfs*38), c.2125C>T (p.Arg709*), c.2175dupA (p.Glu726Argfs*4), c.2290C>T (p.Arg764*), c.2353C>T (p.Arg785*), c.2374C>T (p.Arg792*), c.2490+1G>A, c.2657+5G>A, c.2668C>T (p.Gln890*), c.2739T>A (p.Tyr913*), c.2834C>T (p.Ser945Leu), c.2909G>A (p.Gly970Asp), c.2988G>A (p.Gln996=), c.2988+1G>A, c.3067_3072delATAGTG (p.Ile1023_Val1024del), c.3107C>A (p.Thr1036Asn), c.3140-26A>G, c.3196C>T (p.Arg1066Cys), c.3197G>A (p.Arg1066His), c.3266G>A (p.Trp1089*), c.3276C>A (p.Tyr1092*), c.3276C>G (p.Tyr1092*), c.3294G>C (p.Trp1098Cys), c.3294G>T (p.Trp1098Cys), c.3353C>T (p.Ser1118Phe), c.3454G>C (p.Asp1152His), c.3472C>T (p.Arg1158*), c.3484C>T (p.Arg1162*), c.3528del (p.Lys1177Serfs*15), c.3611G>A (p.Trp1204*), c.3612G>A (p.Trp1204*), c.3659delC (p.Thr1220Lysfs*8), c.3717+4A>G, c.3717+5G>A, c.3718-2477C>T, c.3744delA (p.Lys1250Argfs*9), c.3764C>A (p.Ser1255*), c.3773dupT (p.Leu1258Phefs*7), c.3808del (p.Asp1270Metfs*8), c.3845G>A (p.Trp1282*), c.3846G>A (p.Trp1282*), c.3889dupT (p.Ser1297Phefs*5), and c.3909C>G (p.Asn1303Lys).
Only the mutations listed above will be reported.
Turn Around Time
7 days or fewer
Specimen Requirements and Shipping/Handling
Blood: A single tube with 1-5 mL whole blood in EDTA (lavender top).
Saliva: To request a DNA Mouthwash Collection Kit please contact Genetics Center at (714)288-3500.
Shipping:
Store blood at 4°C until shipment. Ship at ambient temperature in an insulated container via overnight delivery within 96 hours of collection
Send Specimen(s) to:
211. S Main Street
Suite AA
Orange, CA 92868
Tel: (714)288-3500
Required Forms
CPT Codes
CPT’s: 81220, G0452