Poly Thymidine Polymorphism and Cystic Fibrosis in a Non-Caucasian Population

Abstract

Abstract.Background: Cystic fibrosis is a monogenic recessive disorder found predominantly in Caucasian population. This disease arises from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In this study we consider poly T polymorphism c.1210-12T [5], c.1210-12T[7], c.1210-12T[9] (T5, T7, T9) in the intron 8 of CFTR gene in normal individuals and cystic fibrosis patients in the north of Iran. Material and methods: 40 CF patients and 40 normal individuals were screened for poly T polymorphism in intron 8 of CFTR gene using Reverse Dot Blot method which was also used to detect p.Phe508del among CF patients. Results: T7 allele is the most prevalent in both normal and CF patients. Its abundance is approximately 75%. T9 and T5 represent approximately 20% and 5% of alleles respectively. T7/ T7 genotype is the most present in both normal and CF patients with 72.5% and 60% prevalence respectively. p.Phe508del was present in 13 CFTR alleles belonging to 7 patients with either homozygote T9/ T9, T7/ T7 or compound heterozygote T7/ T9 genotypes. Conclusion: Contrary to the Caucasians, T7 allele is more frequent in Northern Iranian CF patients. The presence of p.Phe508del and T7 allele in the same framework is reported for the first time in this part of the world. Further investigations of other populations will help to understand whether p.Phe508del arose by selection pressure in this part of the world or was imported from European countries. The abundance of T5, T7, T9 alleles indicates that this polymorphism can be used as one of the informative markers for detection of normal and mutant alleles in prenatal diagnosis or carrier assessment in families with previous history of the disease in regions with high degree of CFTR mutation heterogeneity.

Identification of the CFTR p.Phe508Del founder mutation in the absence of a polythymidine 9T allele in a Hispanic patient

“…p.Phe508del has always been reported with (TG)10-9T, except in Lebanese Maronites in whom 66.7% of p.Phe508del carriers have the 7T allele (4), and in one North Iranian individual who was homozygous for p.Phe508del and 7T (5). The unusual haplotype we report here is not known to occur in other populations, In the forward sequence tracing, the red peaks represent T and the black peaks represent G. In the reverse sequence, the corresponding nucleotides are A (green) and C (blue).…”

Efficacy and safety of ivacaftor in patients with cystic fibrosis who have an Arg117His-CFTR mutation: a double-blind, randomised controlled trial

“…5 In addition, production of properly spliced CFTR mRNA transcripts is impacted by the length of the cis -localized intron 8 polythymidine (Poly-T) tract. 6 As with CFTR mutations, the 3 common alleles at the poly-T locus, 5T, 7T, and 9T, occur with varying geographic frequency, 7–13 with the 5T variant in cis with R117H-CFTR associated with greater risk for CF disease. 14 Reduced function and variable expression of R117H-CFTR results in residual CFTR ion transport and consequently a variable clinical presentation.…”

Four case reports of Chinese cystic fibrosis patients and literature review

“…Missense occupies 39.57% of the CF mutations and Splicing is responsible for 11.35% of the mutations. p. F508del is the most common mutation, which occurs in approximately 70% of Caucasian CF patients, with other disease‐causing mutations occurring in lower frequencies . The p.F508del is not a common mutation in Asian CF patients.…”