Medical genetics. Contents module 4. Monogenic diseases. Cystic fibrosis (clinical pictures, diagnosis, treatment)

Abstract

Monogenic diseases or genetic diseases (such name is spread abroad) - a group of diseases (with diverse clinical manifestations), which are caused by mutations at the gene level and in most cases have Mendelian inheritance pattern. At the basis of this group of hereditary disease are single gene mutations or point mutations, which include defects of exons (deletions, insertions, substitutions, inversions), defects of introns and flanking parts (change in polyadenylation signal), which leads to changes in the composition and order of nucleotides in the DNA molecule, disorder of genetic information translation from DNA to RNA, from RNA to ribosomes and to changes of the sequence of amino acids in a polypeptide. The following types of human gene mutations that cause hereditary diseases have been described: - Missens; - Nonsense; - Frameshift; - Deletions; - Inserts (inertia); - Disorder of splicing; - Increase in number (expansion) of trinucleotide repetitions. Mutations that cause genetic diseases, may involve structural, transport and embryonic proteins, enzymes. Levels of protein synthesis regulation: - Pretranscriptional. - Transcriptional. - Translational. Cystic Fibrosis is a frequent monogenic disease caused by CFTR (cystic fibrosis transmembrane regulator) gene mutation, characterized by excretory glands affection of vital organs and systems; usually has severe course and prognosis. Cystic Fibrosis (CF) frequency ranges depending on population. CF frequency is from 1:2000 to 1:4000 newborns in countries of Europe and Northern America. Genetics CF is inherited in an autosomal recessive pattern. Since both parents are heterozygotes for abnormal CFTR gene and consequently they are only its carriers, the incidence rate of a child born with CF is 25%. In each subsequent pregnancy, this rate remains unchangeable-«a risk has no memory». CFTR gene was indentified in 1989 year. It contains 27 exons, covers 250000 pairs of nucleotides and is located in the middle of 7 chromosome long arm. More than 1000 gene mutations have been identified, responsible for symptoms development of CF. The most prevalent is AF508 mutation (50-53%).