A specific haplotype framework surrounds the Omani cystic fibrosis transmembrane conductance regulator (CFTR)‎ mutation S549R

Abstract EN

Cystic Fibrosis (CF) is an autosomal recessive disorder affecting the chloride transport in mucus-producing epithelial cells.

The disease is caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR), which is responsible for trans-epithelial chloride transport.

Approximately 1900 mutations and gene variants of the CFTR have been described.

The spectrum of major White-European mutations includes F508del, G542X, G551D and N1303K.

F508del is the most common CF-causing mutation, found in approximately 70% of all CF patients worldwide.

The spectrum of CF mutations of Arab populations is under-investigated.

However, initial molecular-epidemiological studies indicate the existence of specific CF mutation clusters within geographical regions in the Middle East, suggesting specific distributions of CF mutation carrying chromosomes in this part of the world.

We showed that the world-wide rare CF mutation S549R is the predominant disease causing mutation in the Omani population.

We reported that S549R, together with two other identified mutations, F508del and the rare private mutation V392G, are genetically linked to the exonic methionine polymorphism c.1408A>G; p.Met470Val at exon 10 and the intronic dimorphic 4-bp GATT 6-repeat at intron 6, c.744_33GATT[6_8].

We detected three haplotypes in 28 alleles of the Omani CF cohort and 408 alleles of our control cohort of unrelated and unaffected Omani volunteers.

The CF disease associated haplotype consisting of an M allele and a 6-repeat expansion, occurred with an allele frequency of only 0.174 in the normal Omani population.

The discriminative power of the haplotype was attributed to the intronic dimorphic 4-bp GATT 6-repeat.

Furthermore, we found only one mutation, c.1733_1734delTA in the Omani CF cohort which deviated from the rule and shared the most common haplotype, a V allele and a 7-repeat extension, with the normal population.