3849-]T MUTATION AND DISEASE SEVERITY IN CYSTIC-FIBROSIS(10 KB C)

50% of patients with cystic fibrosis (CF) are homozygous for the Delta F508 mutation, but the remainder have at least one of many other less common mutations. The 3849+10 kb C-->T splice mutation seems to be as sociated with less severe disease. We report ten CF patients who are h emizygous for this mutation. Three male patients do not have azoosperm ia (sperm counts 12, 53, and 198x10(6)/mL). Another boy died before CF was diagnosed; his genital tract appeared normal at necropsy. All pat ients had clinically sufficient exocrine pancreatic function. Pulmonar y disease was delayed in onset in most of these patients (range <1 to 16; median 9 years), but then became severe in some, progressing to de ath (in two) and need for transplantation in one. Sweat chloride conce ntration was abnormal (80 mmol/L) in one patient but in others was in the intermediate range (45-65 mmol/L). There was substantial variation in pulmonary disease severity within sibships. These observations sug gest some dissociation in genetically determined severity between diff erent organs. There was some evidence among these patients of a tenden cy for disease of the genital tract to become progressively more sever e. Perhaps sperm banking should be offered to male patients. We specul ate that some normal CF transmembrane conductance regulator is made in patients with this splice abnormality.