Cystic fibrosis (CF) is a chronic, developmental, systemic autosomal recessive genetic disease. It is the most common severe genetic disease in the Caucasian population, with an incidence of approximately 1:2500. The disease is due to the alteration of a membrane protein called CFTR (cystic fibro sis transmembrane regulator) that regulates sodium and chlorine exchanges between the inside and outside of the cell. Dysfunction of the protein causes denser secretions (the dis ease was once called mucoviscidosis), leading to chronic lung damage sustained by a vicious cycle of bacterial infection by opportunists and immune response with the release of chemical mediators of inflammation and lytic enzymes. Ninety percent of patients has pancreatic insufficiency (due to gradual obstruction of the pancreatic ducts resulting in pancreatic fibrosis), for which it is necessary to take pancreatic enzymes to promote digestion; in addition, hepatopathy, diabetes, and congenital bilateral aplasia of the vas deferens (CBAVD) in males may be present. The mode of onset, severity, and course of the disease are variable. Some patients have early onset with severe disease symptoms; others have modest respiratory symptoms with a regular digestive picture. Discordance of clinical CF expression is also present in patients with the same CFTR genotype or pairs of siblings with the disease. This has prompted a search for genes inherited independently of CFTR that could act as modulators of clinical expression of the disease.

In addition to the classical form of CF, there are attenuated phenotype forms, characterized by modest clinical expression and normal pancreatic function, often identified in adult patients; in these cases, the disease affects only one organ, such as the vas deferens with CBAVD causing infertility in males or the pancreas with episodes of recurrent pancreatitis. These forms are now called CFTR-related diseases (CFTR-RD).

The diagnosis of CF is based on typical symptoms or familiality (sick siblings), which must be associated with increased chlorine levels in sweat (positive sweat test), or identification of two mutations in the CFTR gene. However, neonatal screening identifies almost all patients with a classical form of the disease at birth. In CFTR-RD, with a negative or borderline normal sweat test, molecular analysis becomes the only diagnostic tool.

Molecular testing of the CFTR gene should always be combined with appropriate multidisciplinary counseling, and the molecular diagnostic laboratory should work closely with the clinician to ensure that the appropriate tests are per formed for each patient. Guidelines suggest performing sweat and molecular testing for CF in some cases (Table 1).

Table1. Conditions in which molecular testing for cystic fibrosis is suggested

More than 2000 different mutations have been recognized in the CFTR, a medium-sized gene (27 exons). Some of these mutations are more widespread; others are specific to geographical areas or ethnic groups, and most are rare and specific to a few patients. The methods used for the molecular diagnosis of CF can be divided into level I and level II analyses. Level I tests evaluate a restricted panel of the most frequent mutations. In negative cases, methods called scanning (e.g., gene sequencing) are used, which analyze the whole gene (level II tests).

Level I molecular analysis are based on commercial kits or homemade methods that foresee the analysis of the most frequent mutations in the reference region of the laboratory; the detection rate of the first-level molecular analysis is linked to the panel of mutations sought and to the ethnic origin of the analyzed patient.

Level II molecular analysis uses scanning systems that allow the recognition of mutations in coding regions and the border regions between introns and exons involved in the splicing process. The most widespread technique is sequencing by automated instruments. Level II tests reach a higher detection rate (about 95%), but the clinical significance of the molecular result is not always easy to interpret because sometimes new mutations are identified for which it is difficult to establish the causative effect. In CFTR-RD patients, the mutations present are often different from those detect able by commercial kits, so a level I analysis has a lower diagnostic sensitivity than in classical CF patients; further investigation by gene sequencing is almost always necessary in these patients.

Once a new patient with CF or CFTR-RD has been identified, in addition to referral to a clinical referral center, it is important to carry out multidisciplinary family counseling and cascade mutation testing on blood relatives. In the case of couples in which both members are carriers of mutations, the opportunity of prenatal diagnosis can be offered.

اخر الاخبار

اخبار العتبة العباسية المقدسة

قسم حفظ النظام ينهي استعداداته الخاصة بحفل تخرج طالبات الجامعات العاشر

العتبة العباسية المقدسة تنشر أكاليل الزهور ومظاهر الفرح بمناسبة ذكرى ولادة أمير المؤمنين (عليه السلام)

مجمع الشيخ الكليني يواصل تحضيراته لاستقبال المشاركات في حفل تخرج طالبات الجامعات العاشر

وصول المشاركات في فعاليات مهرجان روح النبوة الثقافي النسوي العالمي الثامن إلى كربلاء

المزيد

الآخبار الصحية

ماذا يحدث لجسمك عند تناول الوجبات السريعة يوميا؟

لصحة عظام المرأة.. الشاي أفضل أم القهوة؟

لبناء العضلات وإنقاص الوزن.. ما أفضل توقيت لتناول البيض؟

أطعمة صحية تساعد على التعافي من "الإنفلونزا الخارقة"

المزيد

الآخبار التكنلوجية

دراسة تكشف قدرة الحيتان على سماع الأصوات منخفضة وعالية التردد من مسافة بعيدة

تجربة جديدة: الأسفلت المدعوم بالطحالب يقاوم الحفر ويقلل الانبعاثات الكربونية

تسريبات تكشف ملامح أول هاتف قابل للطي من "أبل"

رصد نوع نادر من القطط في تايلاند للمرة الأولى منذ عقود

المزيد

مواضيع ذات صلة

The Example of Diseases Related to the X Chromosome: Hemophilia A and B

Hemoglobin E: A Structurally Altered Hemoglobin With Thalassemia Phenotypes

The β- Thalassemias

The α- Thalassemias

Hemoglobin Structural Alterations

Transient neonatal diabetes

Permanent neonatal diabetes

Fragile X Syndrome

Polyglutamine Disorders

Monogenic Causes of Diabetes : Glucokinase MODY and pregnancy

Monogenic Causes of Diabetes : Glucokinase MODY

Monogenic Causes of Diabetes: Maturity- onset diabetes of the young