A descriptive study was undertaken to characterize the cystic fibrosis transmembrane regulator gene mutations (CFTR) in the Saudi Arabian cystic fibrosis (CF) population in relation to clinical presentation and demographic and ethnic origin. During the period October 1992 to September 1997, 70 patients from 46 families were diagnosed as having CF, based on a typical clinical picture and sweat chloride levels > 60 mmol/l and were screened for CFTR mutations. Twelve mutations were identified in 34 families, which constitutes 70% of the CF alleles in the study group. Pancreatic insufficiency (PI) was found in the following mutations: 1548delG in exon 10 (15%) which occurred mainly in native Saudi patients in the central province; 3120 + 1G-->A in intron 16 (10%) and H139L in exon 4 (7%), found mainly in native Saudis from the eastern province; delta F508 mutation (13%) which occurred mainly in expatriates of Middle Eastern origin from different provinces; L117X in exon 19 (2%); G115X in exon 4 (2%); 711 + 1G-->A in intron 5 (2%); N 1303K in exon 21 (2%) and 425del42 in exon 4 (1%); I1234V in exon 19 (13%) with a predominance of nasal polyps and a variable degree of PI and lung disease; R553X in exon 11 (1%), with electrolyte imbalance; and S549R in 11 (2%) with pancreatic sufficiency and minimal pulmonary disease. The clinical picture did not differ significantly between patients of different ethnic origins with the same CFTR mutation.
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.
National committees recommend annual influenza vaccination for children ≶ 6 months of age with chronic pulmonary diseases, but several studies have suggested that many high risk children do not receive the vaccine. The purpose of this pilot study was to determine whether the use of structured guidelines for which pulmonary disorders warrant influenza vaccination would increase agreement among physicians on whether specific children should be vaccinated. Hospital records of 73 children with an outpatient appointment during the previous month in the pulmonary, allergy or high risk neonatology clinics were reviewed independently by 4 pediatricians. Two reviewers used a set of specific guidelines in deciding whether influenza vaccination was indicated, whereas the other 2 used unspecified clinical judgment. Interrater agreement concerning the advisability of vaccination was higher between the reviewers using the guidelines (overall agreement, 0.89; kappa = 0.73) than between the reviewers using clinical judgment (overall agreement, 0.68; kappa = 0.31). Even among the 34 children for whom all 4 reviewers thought the vaccine advisable, only 13 (38%) had been vaccinated. Studies to define the risk of severe influenza among children with specific lung disorders are needed, but these guidelines can serve as a starting point for the identification of children who deserve individual consideration for annual influenza vaccination.
