FROM BLOOD STAINS TO THE STUDY OF PATHOGENESIS OF HUMAN HEREDITARY-DISEASES

Cystic fibrosis (CF) is the most common autosomal recessive genetic di sease in Caucasians. More than 500 different mutations have now been r eported in the CFTR gene. All these molecular abnormalities can be ide ntified by scanning the entire sequence of the CFTR gene using differe nt techniques, such as single strand conformational polymorphism (SSCP ), denaturing gradient gel electrophoresis (DGGE) or direct DNA sequen cing. All these mutations can be detected directly from a blood stain, such as a Guthrie card. As illustrated from samples of CF chromosomes from Russia, Belgium, and Brittany (France), the distribution of the non DF508 mutations is highly variable. Some of the clinical symptoms are genetically determined, e.g pancreatic status and the milder forms of CF would be associated with certain mutations. In our experience, CF patients older than 35 years are pancreatic sufficient they bear mi ld alleles, have less severe symptoms with a lower and more delayed ps eudomonas aeruginosa colonisation and a well conserved pulmonary funct ion.