Spectrum of mutations of cystic fibrosis in the 22 Arab countries: A systematic review

Abstract

Cystic fibrosis (CF) is an autosomal recessive genetic disease caused by mutations in the CFTR gene, with various clinical manifestations that affect pulmonary, digestive, exocrine and male reproductive functions as well as the bones and kidneys. This study aimed to reveal the spectrum of CFTR gene mutations in Arab CF patients and their corresponding clinical phenotypes among the 22 Arab countries. We searched four literature databases (PubMed, Science Direct, Web of Science and Scopus) from their times of inception to January 2018. All possible search terms were used to encompass the different clinical phenotypes, disease incidences, CFTR mutations, ages and consanguinity rates of CF patients in the 22 Arab countries. Our search strategy identified 678 articles; of these, 72 were eligible for this systematic review. We retrieved data from 18 Arab countries; only 1766 Arab patients with CF were identified, even after additional searches using Google and Google Scholar. The search uncovered a wide spectrum of mutations, some of which are shared with other ethnic groups and some unique to Arab patients. Although the clinical phenotypes of Arab patients were typical of CF, several distinct phenotypes were reported. Despite the rarity of genetic epidemiological studies of CF patients among the 22 Arab nations, the disease is frequently reported in Arab countries where consanguineous marriage is common. Therefore, significant attention should be paid to this problem by implementing carrier and premarital screening, newborn screening and genetic counselling.

Newborn Screening for CF across the Globe—Where Is It Worthwhile?

“…Beyond variability in carrier frequency, the wide range observed in incidence may be in part explained by under-diagnosis and under-reporting of cases [75,76]. The incidence of CF in Asia may therefore be under-estimated.…”

“…In Arab countries, the major challenges are to improve the diagnosis and the detection of mutations before irreversible organ damage has developed and to promote the constitution of national registries [75,76], which will help to improve CF management and health policy planning. To the best of our knowledge, no CF NBS program is implemented to date in the Arab world, but CF NBS is promoted by the annual meeting for NBS in the Middle East and North Africa.…”

“…In view of the high incidence of CF in some Arab countries and the genomic revolution that is underway in those countries (through the Saudi, Qatar, and Emirati genome projects), CF NBS should be worthwhile in the regions where CF is well managed. NBS programs would have to take into account the genetic specificities of that population (limited mutation spectrum, lower prevalence of p.Phe508del mutation, mutations found only in that population [76]) but also the high consanguinity rate.…”

Molecular Diagnosis and Genetic Counseling of Cystic Fibrosis and Related Disorders: New Challenges

“…The monumental interest of the triple-combination is that a large proportion of patients with CF are eligible for treatment in numerous populations. However, in specific ethnic groups, F508del is absent (such as Iraq, Sudan, Qatar, Japan and China) or extremely rare (Jordan 6%–7%, Bahrain 8%) [ 37 ] ( Table S1 ). The challenge is thus to make personalized therapy accessible to all patients.…”

Cystic fibrosis vigilance in Arab countries: The role of genetic epidemiology

“…In a recent publication in Respirology , Al‐Sadeq et al . present a commendable systematic review of the spectrum of CF mutations in the 22 Arab countries . Seventy‐two studies were identified that document disease in 5481 patients and 45 families, in whom a total of 115 mutations were recognized.…”