Rare CFTR Mutation Cell Collection Protocol (RARE)

Inclusion Criteria:

• Male or female ≥ 12 years of age at time of consent

• Documentation of a CF diagnosis as evidenced by one or more clinical featuresconsistent with CF and one or more of the following criteria (1. Sweat chloride ≥ 60milliequivalents/Liter (mEq/L) by quantitative pilocarpineiontophoresis test (QPIT)OR upon permission of the RARE Investigator- Sponsors, 2. Two well-characterizedmutations in the cystic fibrosis transmembrane conductive regulator (CFTR) gene, 3.Abnormal nasal potential difference (NPD) (change in NPD in response to a lowchloride solution and isoproterenol of lessthan -6.6 mV)

• Confirmed genotype of the current recruitment focus for certain target raremutations. The initial recruitment focus will be CF patients who are homozygous forpre-mature stop codons. Operations Memos will detail any future current genotypetargets.

• Written informed consent (and assent when applicable) obtained from participant orparticipant's legal representative and ability to comply with the requirements ofthe study.

• Willing to travel (if needed) to a regional study site for cell collection.

Exclusion Criteria:

1. Presence of a medical condition, abnormality, or laboratory value(s) that in theopinion of the onsite principal investigator and/or collaborating gastroenterologistmay compromise the quality of the data or place the subject at significant risk byundergoing the research related biopsy, including: Significantly diseased distal rectal/GI tissue that could place the participant atrisk by participating in the study (as judged by the collaboratinggastroenterologist, such as significant hemorrhoids, vascular abnormalities, colonicinfection, radiation injury or history of radiation therapy to the rectum, prostateand/or pelvic area) Any of the following abnormal lab values at the study visit: i. Platelets < 50 x 10^3/µL ii. Hemoglobin < 10 gm/dL iii. Hematocrit < 30% iv. WBC > 20 x 10^3/µL v. Neutropenia (ANC < 1.5 x 10^3/µL) vi. Lymphopenia (absolutelymphocyte count < 1.5 x 10^3/µL) vii. PT/INR > 1.5 viii. Other bleeding diathesis

2. Positive pregnancy test (for female of childbearing potential) at the study visit.

3. Breastfeeding (if patient opts to use sedation).

4. Current use of drugs with significant risks of compromising immunity (e.g. oralsteroid use >20 mg/day) for >14 days prior to the rectal biopsy.

5. History of organ transplant.

6. Use of oral anticoagulant medications (e.g., chronic anticoagulant therapy such aswarfarin or platelet inactivators such as aspirin) within seven days prior to rectalbiopsy.

7. Unable or unwilling to withhold use of oral anticoagulant medications (e.g., chronicanticoagulant therapy such as warfarin or platelet inactivators such as aspirin)within 7 days after rectal biopsy.