Genotypephenotype Correlation

Identification of the CF gene, designated CFTR for ''cystic fibrosis transmembrane conductance regulator,'' occurred in 1989.[1,2] It encodes a membrane-embedded ion-channel protein responsible for transport of sodium and chloride. The gene is 230 kbp long, encompassing 27 exons that produce an mRNA of 6500 nucleotides.

Gene sequencing in an initial series of affected patients revealed a recurring deletion, a three-nucleotide mutation of codon 508, which specifies phenylalanine in the protein product.[2] This mutation, now designated AF508, has come to be known as the most prevalent (approximately 70% of Caucasian carriers) and ''classical'' CF mutation. It is generally associated with severe disease, including pancreatic insufficiency, although this is not always the case. Since that original discovery, we have come to appreciate the remarkable molecular heterogeneity of CF, perhaps the most dramatic of any Mendelian disorder under study. There are now over 1000 mutations documented in the CFTR gene ( CFTR), and the range of clinical manifestations can be quite wide. Unfortunately, attempts to predict disease severity based on genotype have been frustratingly inconsistent, making genetic counseling for couples at risk rather difficult. Although some mutations are less likely to cause pancreatic insufficiency,1-3-1 there are exceptions to all of the rules. Even the classic AF508 mutation may not always produce severe lung disease, even in the homozygous state.[4]

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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