P67L: a cystic fibrosis allele with mild effects found at high frequency in the Scottish population

• Published in: Journal of medical genetics Vol. 35; no. 2; pp. 122 - 125
• Main Authors: Gilfillan, A, Warner, J P, Kirk, J M, Marshall, T, Greening, A, Ho, L P, Hargreave, T, Stack, B, McIntyre, D, Davidson, R, Dean, J C, Middleton, W, Brock, D J
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01.02.1998; BMJ; BMJ Publishing Group LTD
• Subjects: Adolescent; Adult; Alleles; Biological and medical sciences; Child; Cystic Fibrosis - diagnosis; Cystic Fibrosis - epidemiology; Cystic Fibrosis - genetics; DNA - analysis; Exocrine Pancreatic Insufficiency - physiopathology; Female; Gene Frequency - genetics; Gene Frequency - physiology; Genes, Dominant; Genetics, Population; Health Surveys; Heterozygote; Humans; Infant; Male; Medical sciences; Mutation; Pneumology; Respiratory system : syndromes and miscellaneous diseases; Scotland - epidemiology; Sweat - chemistry; United Kingdom; Scotland; Great Britain; Europe; Human; Respiratory disease; Clinical form; Metabolic diseases; Genotype; Cystic fibrosis; Genetic determinism; Genetic disease; Heterozygosity; Compound heterozygosity; Allele; Phenotype; Digestive diseases; Genetics; Dominant character; Pancreatic disease
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.35.2.122

Only three mutant cystic fibrosis (CF) alleles have to date been established as conferring a dominant mild effect on affected subjects who are compound heterozygotes. We now add a fourth, P67L, which occurs on about 1.4% of Scottish CF chromosomes. Among 13 patients (12 unrelated) with this allele, the average age at diagnosis was 22.5 +/- 11.3 years. None of the cases had consistently raised sweat chloride concentrations, the average value being 57 +/- 9 mmol/l; 77% of the patients were pancreatic sufficient. When compared to three other established mild CF alleles, R117H, A455E, and 3849 + 10kb C-T, a compound heterozygote for P67L has minimal disease and clinical suspicions are unlikely to be confirmed other than by DNA typing.