Genotype patterns for mutations of the cystic fibrosis transmembrane conductance regulator gene: a retrospective descriptive study from Saudi Arabia.

BACKGROUND: Cystic fibrosis (CF) occurs in populations in Saudi Arabia and the Gulf area. Approximately 2000 known variants have been identified for the CF transmembrane conductance regulator (CTFR) gene. Screening for ten of the most common variants can detect 80% of alleles. OBJECTIVE: Determine the pattern of CFTR variants in the CF population of Saudi Arabia. DESIGN: A retrospective, descriptive. SETTING: Tertiary care center. PATIENTS AND METHODS: We examined the medical records of 396 confirmed CF patients of all age groups that were positive for a CFTR variant from the period of 1 January 1998 to 1 December 2017. MAIN OUTCOME MEASURES: Zygosity, morbidity and mortality patterns of different types of CFTR variants. SAMPLE SIZE: 312 families that included 396 patients. RESULTS: Of 48 variants identified, 6 were novel, having not been described in the medical literature. A homozygous state was found in 283 families (90.7%) and compound heterozygosity in 23 (7.4%). Six families were heterozygous (1.9%). Median age (interquartile range) was 10.2 months (4.4 months to 5.7 years) at diagnosis and 9.7 (5.4-16.5) years at follow up. Of 396 patients, 378 patients (95.5%) survived and 18 (4.5%) died. The ten most common variants identified in descending frequency were: p.Gly473GlufsX54 in 98 alleles (16%), p.Ile1234Val in 66 alleles (11%), F508del in 64 alleles (11%), 711+1G>T in 62 alleles (10%), 3120+1G>A in 62 alleles (11%), p.His139Leuin 38 alleles (6.4%), p.Gln637Hisfs in 30 alleles (5.2%), p.Ser549Arg in 27 alleles (4.5%), p.Asn1303Lys in 14 alleles (2.3%), delExon19-21in 10 alleles (1.6%). This analysis identified 79.2% of our CFTR variants. CONCLUSION: CFTR mutational patterns in our CF population are characterized by a high allelic heterogeneity. The high prevalence of homozygous variants reflects the high level of consanguinity between parents. LIMITATIONS: Our CFTR screening reflected only about 80% of CF patients in Saudi Arabia. CONFLICT OF INTEREST: None.

Clinical profile of Saudi children with bronchiectasis.

OBJECTIVE: This study represents the experience of a tertiary care center in Saudi Arabia on non-cystic fibrosis bronchiectasis. METHODS: A retrospective review of all patients with confirmed Non-Cystic Fibrosis (Non-CF) bronchiectasis by chest X-ray and or CT chest in a pulmonary clinic for the period 1993-2005 at a tertiary care center in Riyadh. RESULTS: A0 total of 151 cases were diagnosed as Non-CF bronchiectasis. Siventy-five (49.7%) were males, 76(50.3%) were females. One hundred forty-eight (98%) are alive and 3(2%) died. The southwestern regions constituted 72(50%) of the cases. There is a period (5+/- 3.2) years between the start of symptoms and the diagnosis of bronchiectasis. More than 2/3 of the patients had cough, tachypnea, wheezing, sputum production and failure to thrive. Ninety one (60%) had associated disease: Pulmonary diseases in 48(32%), immunodefficiency in 27(18%), CNS in 18(12%), cardiac in 12(8%) and asthma in 103(68%) of the patients. Left lower lobes were commonly involved in 114(76%) cases. Sixty-eight (67%) were found to have sinusitis. Forty-nine (32%) developed gastroesophgeal reflux (GER). Hemophilus influenza was cultured in 56(37%), Strept pneumoniae in 25(17%) and Pseudomonas aeruginosa in 24(16%) of the patients. 80% of the patients who had pulmonary function test had abnormal changes. Disease progression was related to development of symptoms before 5 years of age, persistent atelectasis and right lower lobe involvement (p<0.05). CONCLUSION: Non-CF bronchiectasis is a common problem in Saudi Arabia. Early recognition and institution of treatment with proper vaccination of available anti-bacterial and anti-viral vaccines are encouraged to prevent progression of the disease.

A review of 151 cases of pediatric noncystic fibrosis bronchiectasis in a tertiary care center.

OBJECTIVE: This study was conducted to review the etiological factors and diseases associated with pediatric noncystic fibrosis bronchiectasis in a tertiary care center in Saudi Arabia. MATERIALS AND METHODS: A retrospective review of all patients with confirmed noncystic fibrosis (Non-CF) bronchiectasis by chest X-ray and/or CT chest in a pulmonary clinic during the period 1993-2005 at a tertiary care center in Riyadh. RESULTS: A total of 151 cases were diagnosed as Non-CF bronchiectasis. Seventy-five (49.7%) were male, 76 (50.3%) were female; 148 (98%) are alive and 3 (2%) died. The southwestern regions constituted 72 (50%) of the cases. There was a period of (5 +/- 3.2) years between the start of symptoms and diagnosis of bronchiectasis. More than two-thirds of the patients had cough, tachypnea, wheezing, sputum production and failure to thrive. Ninety-one (60%) had associated diseases: Pulmonary diseases in 48 (32%), immunodeficiency in 27 (18%), central nervous system anomalies in 10 (7%), cardiac in 10 (7%) and asthma in 103 (68%) of the patients. Left lower lobe was commonly involved in 114 (76%) patients. Sixty-eight (67%) were found to have sinusitis. More than two-thirds of patients had two or more associated diseases. Forty-nine (32%) developed gastroesophageal reflux. Hemophilus influenza was cultured in 56 (37%), strep pneumoniae in 25 (17%) and pseudomonas aeruginosa in 24 (16%) of the patients. Eighty percent of the patients who had pulmonary function test had abnormal changes. Disease progression was related to development of symptoms before 5 years of age, persistent atelectasis and right lower lobe involvement (P< 0.05). CONCLUSION: Non-CF bronchiectasis should be included in the differential diagnosis of recurrent chest infection in Saudi Arabia. Early diagnosis and identification of associated diseases is needed to prevent progression of the disease.