[DNA analysis and prenatal diagnosis in cystic fibrosis]

Abstract

Cystic fibrosis (CF) is the most common autosomal recessive lethal genetic disorder in man, affecting 1 in 2,000 live births. The carrier frequency in Caucasians is 1 in 20. Approximately 70 per cent of the mutations correspond to a specific deletion on chromosome 7 (region 7q31). This delta F 508 mutation of the CF gene results in the loss of phenylalanine at position 508 in the gene product. About 50 per cent of the individuals with CF are homozygous for this deletion and suffer from pancreatic insufficiency. The remaining half are mostly compound heterozygotes between this deletion and another mutation. They exhibit less severe symptoms. Several simple polymerase chain reaction (PCR) tests are available to detect the delta F 508 mutation, allowing rapid prenatal diagnosis of the disease. In those families where other mutations of the CF gene are involved prenatal diagnosis is performed by means of tightly linked restriction fragment length polymorphisms (RFLPs). PCR tests are available for RFLP analysis too. Testing for the delta F 508 deletion, present in about 3 per cent of the normal population, may prove invaluable for extensive carrier screening. Thus, half of the couples at risk could be recognized before the first affected child is born.