title: 3849+10 kb C-->T mutation and disease severity in cystic fibrosis.
abstract: 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 associated with less severe disease. We report ten CF patients who are hemizygous for this mutation. Three male patients do not have azoospermia (sperm counts 12, 53, and 198 x 10(6)/mL). Another boy died before CF was diagnosed; his genital tract appeared normal at necropsy. All patients had clinically sufficient exocrine pancreatic function. Pulmonary 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 death (in two) and need for transplantation in one. Sweat chloride concentration 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 suggest some dissociation in genetically determined severity between different organs. There was some evidence among these patients of a tendency for disease of the genital tract to become progressively more severe. Perhaps sperm banking should be offered to male patients. We speculate that some normal CF transmembrane conductance regulator is made in patients with this splice abnormality.
authors.affiliation: Leroy W Matthews Cystic Fibrosis Center, Department of Pediatrics, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: R C
authors.initials: RC
authors.lastname: Stern
authors.forename: C F
authors.initials: CF
authors.lastname: Doershuk
authors.forename: M L
authors.initials: ML
authors.lastname: Drumm
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D003550:Cystic Fibrosis / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005808:Genes, Recessive; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D009845:Oligospermia / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length; D012326:RNA Splicing / Q000235:genetics*; D012720:Severity of Illness Index