CFTR Gene Mutations in the Egyptian Population: Current and Future Insights for Genetic Screening Strategy

Cystic Fibrosis (CF) is the most common lethal rare genetic disease in the Caucasian populations. It is caused by a variety of sequence alterations in the Cystic Fibrosis Transmembrane Regulator (CFTR) gene. In Caucasian, one over 3,500 new born children suffers from the disease and one over 30 of them is at least carrier of a severe mutation in the CFTR gene. CF and CFTR-related disorders (CFTR-RDs) are two distinct clinical outcomes of the gene mutations. The CF mutation induces a severe phenotype involving different organs, whereas a CFTR-RD mutation induces less life-threatening symptoms with three main clinical entities including congenital bilateral absence of the vas deferens (CBAVD), acute recurrent or chronic pancreatitis, and disseminated bronchiectasis (Bombieri et al., 2011). In the Arab countries, the spectrum of CF mutations, incidence and prevalence of the disease are largely unknown in the Arab populations (Wei et al., 2006). This is due to the lack of disease awareness, and diagnosis facilities that mislead the identification of CF during many decades. Additionally, epidemiological studies that realized were revealed a distinguished mutational spectrum between Arab countries if compared to White-European populations. Furthermore, Arab Mediterranean countries have a different CFTR mutational profile if compared to the Arabian Peninsula. Egypt as Mediterranean North African country, this strategic position attracted many invaders throughout its history. Therefore, in addition to its Pharaonic origin, gene flow to its population occurred from the Ethiopian, Greco-Roman, Arab, Turkish, French and English settlers (Temtamy et al., 2010). The common heritage among the countries bordering the Mediterranean is not restricted to historical or cultural aspects. There are considerable commonalities in the gene pools of the Mediterranean Northern and Southern countries. This " genetic sharing " has resulted from considerable human movements (i.e., migration, invasion, and trade) throughout history in this area (Temtamy et al., 2010). Consequently, Egypt is not like other Arab countries and mutations in the CFTR gene have been influenced by gene flow coming from different populations. Furthermore, the high rate of consanguinity, infant and neonatal mortality in the Egyptian society will, therefore, increase CF incidence and private mutations. Indeed, another important issue is the increase number of CFTR-related disorders patients such as idiopathic bronchiectasis, congenital bilateral absence of the vas deferens, idiopathic (non-alcoholic) pancreatitis, and severe sinusitis in the Egyptian population. This observation is in agreement with data previously published (Lissens et al. In Egypt, there is no available data on …