Cystic fibrosis can skip a generation

Cystic Fibrosis (CF)

Synonyms

Cystic fibrosis

Clinical symptoms

The Cystic fibrosis or Cystic Fibrosis (CF) is one of the most common autosomal recessive inherited diseases in the Caucasian population. It is caused by functional disorders of a chloride ion channel in the cell membranes of the glandular epithelia. This leads to an increased salt content in sweat and the formation of viscous secretions in other organs. This mainly affects the respiratory tract (recurrent bronchopulmonary infections), the gastrointestinal tract (failure to thrive, diarrhea and exocrine pancreatic insufficiency).

Cystic fibrosis can manifest itself prenatally or after birth through a meconium ileus. An early manifest chronic pancreatitis can also be caused by CF mutations.

Congenital bilateral aplasia of the vas deferens (CBAVD) leads to infertility in males.

In addition to the classic early manifestations, forms with a later onset or initially milder or atypical symptoms are increasingly observed. With regard to optimal care of those affected and in particular the prophylaxis and treatment of infections of the respiratory tract, which essentially determine the patient's prognosis, early diagnosis is extremely important.

genetics

The responsible gene CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) is on chromosome 7q31.2. Cystic fibrosis is inherited as an autosomal recessive trait. If two healthy carriers are in a partnership, there is a 25% chance of having a child with CF.

In Central Europe the mutation is p.Phe508del (F508del) the most common at 75%. The amino acid phenylalanine in codon 508 is lost here. Of the remaining disease-causing mutations, only a few reach a frequency of 1-2% in Central Europe.

Since the mutation spectrum of different ethnic population groups differs significantly, the indication of the ethnic origin is important for the assessment.

frequency
  • In Central Europe: 1: 2,000 - 1: 2,500
  • Carrier: 1:22 - 1:25
indication
  • O. g. Symptoms such as meconium ileus, failure to thrive, recurrent bronchopulmonary infections, abnormal sweat test and male infertility
  • Clarification of the carrier status, especially in families at risk
  • Prenatal diagnosis with proven carrier status of both parents
Stage diagnostics
Sequence analysis according to Sanger (coding and adjacent areas)
MLPA, Multiplex Ligation dependent Probe Amplification

Method for the detection of deletions / duplications of individual exons

Sequence analysis of at least 35 common mutations of the gene CFTR (Frequency by ethnic origin> 1%) and possibly MLPA
Sanger sequence analysis of the remaining regions of the gene CFTR and possibly MLPA
Material 2-4 ml EDTA blood