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Cystic Fibrosis, CF - CFTR

Mucoviscidosis

Clinical Features

Cystic fibrosis is one of the most common autosomal recessive diseases in the Caucasian population. It is caused by functional defects of a chloride ion channel in cell membranes of glandular epithelias. The salt content in sweat increases (sweat chloride test as important diagnostic criteria) and abnormally thick, sticky mucus is formed in other organs. This applies in particular to the respiratory tract (repetitive bronchiopulmonary infections), the gastrointestinal tract (failure to thrive, diarrhea and exocrine pancreatic insufficiency). Early manifestations of chronic pancreatitis can also be caused by CF mutations. Meconium ileus may be a prenatal or early postnatal sign. The congenital bilateral aplasia of the vas deferens (CBAVD) results in male infertility (cf. paragraph on CBACD). Besides the classic early manifestations, subtypes with later onset or with atypical and less severe symptoms are increasingly recognized. In order to ensure optimal care for the affected individuals, early diagnosis is of utmost importance, especially with regard to the prophylaxis and treatment of pulmonary infections which critically determine the patients' prognosis.

Genetic Information

The responsible CFTR gene (cystic fibrosis transmembrane conductance regulator gene, is located on chromosome 7 (7q31.2). Cystic fibrosis is an autosomal recessive disease. The children of two healthy carriers will have a 25% risk to develop CF.

In Middle Europe and in the Caucasian population of North America, the mutation F508del leading to the loss of the amino acid phenylalanine at codon 508 is responsible for approximately 75% of CF cases. Around 50% of the affected individuals in Germany carry two alleles of this mutation (homozygosity for F508del). The remaining pathogenic mutations are hardly more frequent than 1-2%. Mutation spectrum and mutation detection rates vary significanltly among different population groups. Therefore, knowledge of ethnic background of the patient is highly important for genetic risk estimation.

Prevalence

1 : 2 000 to 1 : 2 500 in the Middle European population; every 22nd to 25th person in the caucasian population is a healthy carrier for one CF allele.

Diagnostic