Understanding Pulmonary Cystic Fibrosis

Abstract

The genetic basis for cystic fibrosis is well-characterized, severe monogenic recessive disorder, that arises from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.There are several molecules that interact with CFTR gene, such as ORCC, ENaC, ROMK2, Aquaporin 3 (AQP3), NKCC1, NBC-1, Syntaxin 1A, and NHERF/EBP50. The ORCC molecule outwardly rectifies the chloride channel. Since 1989, more than 1,500 specific gene mutations and DNA sequence variations have been identified in CFTR gene. The Delta F508 mutation is the most common and is identified in almost all racial and ethnic groups ( approximately 70% of all cystic fibrosis genes). The sweat ducts of the patients are impermeable to the chloride ions, thus, the sodium chloride remains in the secretions contributing the salty sweat.Typical symptoms includes salty-tasting skin, wheezing or shortness of breath, frequent lung and par nasal sinus infections, nasal polyps, poor growth and poor weight gain, swollen belly accompanied by abdominal gas and discomfort, and broadening of the fingertips and toes. A sweat chloride concentration of more than 60 mmol/liter determined on two or more occasions by quantitative pilocarpineionophoresis remains the “gold standard” for diagnosis, but false-negative sweat tests can also be a consequence of the particular combination of CFTR mutations carried by an individual cystic fibrosis patient. The genetic testing is available, but is not commonly used because it cannot detect all gene mutations ( approximately 70-75% of the detection rate).