Molecular Genetics Cystic Fibrosis, CFTR, Screening

Cystic Fibrosis (CF) is the most common autosomal recessive genetic disease in the Caucasian population appearing in approximately one in every 2,500 newborns.  In the Caucasian and Ashkenazi Jewish populations, about one in every 25 individuals carries one copy of a mutation in the CFTR gene at 7q31.2.

Reasons for Referral:

• Confirmation of clinical diagnosis
• Carrier identification in persons with a positive or negative family history
• Reflex testing for newborn screening
• Testing of Sperm & egg donors
• Abnormal fetal ultrasound
• Preconception and carrier screening

Direct Mutation Analysis:  Bead-based array methodology tests for 60 CFTR variants including all of the variants in the ACMG/ACOG-recommended mutation panel:

ACMG/ACOG panel

ΔF508	R553X	R117H	1898+1G>A	R1162X	711+1G>T	ΔI507
G542X	621+1G→T	R334W	2184delA	3659delC	2789+5G>A	G551D
N1303K	R347P	1717-1G→A	W1282X	A455E	R560T	G85E
3120+1G→A	3849+10kbC→T

Additional variants:

1078delT	394delTT	Y122X	R347H	V520F	A559T	S549N
S549R(T>G)	1898+5G>T	2183AA>G	2307insA	Y1092X	M1101K	S1255X
3876delA	3905insT	E60X	R75X	406-1G>A	G178R	L206W
935delA	G330X	Q493X	1677delTA	2055del9>A	2143delT	K710X
3791delC	Q890X	3199del6	R1066C	W1089X	D1152H	R1158X
CFTRdele2,3	S1196X

Additionally, 5T/7T/9T tract is reported for R117H carriers. Reflex testing for I506V and I507V is performed only when indicated.

Mutation Analysis:
      91% detection in the Caucasian/non-Ashkenazic population
      96% detection in the Ashkenazic population
      73% detection in the African-American population
      84% detection in the Hispanic-American population
      55% detection in the Asian-American population

Test reporting follows the American College of Medical Genetics (ACMG) guidelines.

 Blood: Lavender tube (EDTA) or yellow (ACD)

• Adult: 6.0 mL
• Child: 6.0 mL
• Infant: 2.0 mL

Saliva: 2 ORAgene Saliva Kit(s) (OGR-500) used according to manufacturer instructions. Please contact KDL Client Services for a Saliva Collection Kit for patients that cannot provide a blood sample.

Assisted Saliva: 4 ORAgene™ Assisted Saliva Collection Kits (OGR-575) used according to manufacturer instructions. Please contact KDL Client Services for an Assisted Saliva Collection Kit for patients that cannot provide a blood sample.

DNA: 50ng at a minimum of 10ng/µL

Prenatal:

• Direct Amniotic Fluid (10-20mL)
• Direct CVS
• Direct POC
• Cultured Amnio (2-T25 flasks)
• Cultured CVS (2-T25 flasks) 
• Cultured Fetal Tissue: Product of Conception (2 T-25 flasks)
• Cord blood

Notice Regarding Molecular Genetic Testing on CVS or Amniotic Fluid Specimens:

• Maternal cell rule-out testing will be performed on all prenatal specimens received.  Pease provide maternal blood in addition to the fetal specimen.  Additional charges apply for the maternal cell rule-out test.

For routine testing of blood, saliva and buccal swabs, KDL does NOT accept samples from patients within two (2) weeks of a packed cell/platelet transfusion or within four (4) weeks of a whole blood transfusion.  For extraordinary circumstances, where testing must be performed outside of the above windows, please contact our lab.

A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES.  Please include detailed clinical information, including ethnicity, clinical history, and family history.

Weekly

7-10 days

• Keep specimen cool during transit, but do not ship on dry ice. 
• Please use the cold pack provided in the KDL shipping kit. 
• Ship the specimen overnight express, using the FedEx priority overnight label provided. 
• Please contact Client Services at (855) 535-1522 for shipping kits and instructions.

1. Schneider M. et al, 2007  Clin Genet 72:30-38.

Full CFTR Sanger sequencing and MLPA for large deletions and duplications tests are also available.

Prior to any genetic testing we recommend genetic counseling. To receive forms and information about prenatal diagnostic testing, please contact Client Services at (855) 535-1522.