الفهرس 
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Abstract
Cystic fibrosis (CF) is the most prevalent, fatal, autosomal recessive disease affecting Caucasians . A variety of mutations in the CFTR gene are the cause of cystic fibrosis. One in every 3,500 Caucasian newborns is affected by the condition, and one in every 30 of them is at least a carrier of a severe CFTR gene mutation. The CFTR gene has more than 2000 different reported mutations. at least 1500 of them are thought to be CF-causing mutations as they are reported in patients with symptoms of CF. They are categorized into 6 classes based on their effect on the synthesis and/or function of the CFTR protein. Since cystic fibrosis is the most common lethal autosomal recessive disease in Caucasian population , screening for carriers in the family members will be beneficial for early prevention and treatment, and also will give a chance for prenatal screening and diagnosis.The aim of the work:Screening of common and rare genetic mutations of CFTR gene in Egyptian families with cystic fibrosis children to identify asymptomatic cases and carrier state for early intervention and preventive strategy.Type of study: cross sectional study.Materials and Methods:This is a cross sectional study of 35 cystic fibrosis children among 27 families who were diagnosed as cystic fibrosis based on clinical criteria , sweat chloride test and genetic testing . They were enrolled from the Genetics and GIT units in Mansoura University Children Hospital. Blood samples were obtained from the case , parents, and at least one sibling. They were screened for the presence of the 8 common and 16 rare mutations in Caucasians by RT-PCR.We used cystic fibrosis REAL-TIME PCR genotyping kits intended for detection of the 8 common CFTR gene mutations ( F508del – E92K – W1282X – N1303K – 2143delT – 1677delTA – 3849+10kbC>T – dele2,3(21kb) )And the 16 rare genetic mutations ( L138ins – G542X – R117H – 604insA - 621+1G>T – S1196X – 3821delT – 3667insTCAA – R334W - 394delTT – R553X – K598ins – 2184insA – 2183AA>G – 2789+5G>A – 3944delGT)•Method: REAL-TIME PCR followed by melting curve analysis and qualitative analysis. our children aged from 3 months up to 14 years , median age is 4.5 y , mean age is 5.3 y, 57% of patients are below 5years ,65.7% are males, and 71.4% are from rural areas.total number of affected children : 35 child in 27 families. 51.4% are diagnosed before 1year, mean age at diagnosis is 1.9 y ,median age at diagnosis is 9.5 m.The most frequently affected system in our study is the GIT in 94.3% of patients, 68.6% have respiratory symptoms, 80% of patients show failure of growth , 8.6% of patients have history of meconium ileus , and 11.4% of patients suffer from chronic liver disease.60% are born to consanguineous parents, the most common mutation detected is F508del in 79.9% of patients, followed by W1282x and 2183AA>G each in 5.7% of patients, 51.4% of patients are affected with homozygous mutation.The pattern of inheritance is autosomal recessive in 51.8% of families while 48.2% of families have other CF mutations in their children that are not detected in parents.Conclusion:•The mean age at diagnosis in our study was about 2 years of age, with male to female ratio of 1.9:1.•The most frequent symptoms were GIT symptoms and failure to thrive followed by respiratory symptoms.•Patients diagnosed earlier had more severe manifestations of the disease.•The most frequently encountered mutation was F508del, followed by W1282x and 2183AA>G .•No significant relationship was found between genotype of the patients and phenotype of the disease.•When parents were consanguineous , there was higher risk for both of them to be carrier , and higher risk for their cystic fibrosis children to be homozygotes .Recommendations:•Genetic counseling and screening of families with cystic fibrosis children is recommended for detection of carriers and asymptomatic cases for early intervention and preventive strategy.•Screening should include sweat chloride testing and real time PCR for detection of common and rare mutations of CFTR gene.•In doubtful conditions , DNA sequencing may be used to identify other mutations of CFTR gene which may be known to cause CF, or may be novel mutations .Key words: cystic fibrosis, CFTR gene, family screening.