Tehran University Medical Journal

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Background: Cystic fibrosis (CF) is a multiorgan autosomal recessive disorder. As CF is highly heterogeneous in Iran and many mutations have a low frequency, routine molecular diagnostic methods are not very efficient. The use of highly polymorphic intragenic markers not only can facilitate phenotype prediction in prenatal diagnosis by gene tracking, but also can lead to the demonstration of possible associations between haplotypes and specific mutations. We determined IVS8 polyT and M470V polymorphisms in exon 10 of CFTR gene in this case-control study.

Methods: Polymorphisms of IVS8 polyT in 53 patients with CF were referred to Amirkola children's Hospital of Babol University of Medical Sciences, 2007 to 2011 and 49 fertile healthy individuals were determined by reverse dot blot method. M470V polymorphism was analyzed by PCR-RFLP.

Results: In IVS8 polyT study, T7 was the most frequent allele in healthy individuals than patients with CF (respectively, 82.8% Vs. 77.2%). T9 was more abundant in patients with CF than normal individuals (respectively, 21.7% Vs. 7.4%, P=0.005). T9/T9 genotype was more frequent in patients than healthy individuals (respectively, 15.1% and 2%, P=0.032). Study for M470V polymorphism showed that M/V was the most common genotype in normal individuals and patients with CF (respectively, 49% and 40.4%). M-T9 haplotype was highly associated with the disease in both patients with CF and normal individuals (respectively, 19.1% and 2.4%, (P<0.001)

Conclusion: The allelic distribution and heterozygosity results suggest that both M470V and IVS8 polyT can be helpful in the prenatal diagnosis of CF in Northern Iranians with a positive family history of the disease.

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Background: Medullary thyroid carcinoma (MTC) occurs in both sporadic (75%) and hereditary (25%) forms. The missense mutations of the rearranged during transfection (RET) proto-oncogene in MTC development have been well demonstrated. Several studies have been published that indicate the molecular analysis of RET gene may offer early identification of those patients at high risk to develop MTC and may provide the opportunity for early intervention. The aim of this study was to investigate frequency of G691S/S904S haplotype in MTC patients and their relatives. Methods: From 2004 to 2014, 358 participants were studied, including 213 patients (119 female, 94 male) and 145 their relatives (79 female, 66 male) in cellular and molecular research center of Shahid Beheshti Research Institute for Endocrine Sciences, Tehran, Iran. Genomic DNA was extracted from peripheral blood leucocytes using the standard Salting Out/Proteinase K method. Nucleotide change detection was performed using PCR and direct DNA sequencing methods. The RET mutations and SNPs, sequences were analyzed. Results: According to DNA sequencing results, 189 individuals (119 patients, 70 relatives) had both G691S (rs1799939) missense mutation in exon11 and S904S (rs1800863) synonymous mutation in exon 15 of RET proto-oncogene. The allele frequency of G691S/S904S haplotype was 35.02% in patients and 29.92% in their relatives. Conclusion: The obtained data showed the frequency of G691S/S904S RET gene haplotype among Iranian MTC patients and their relatives. The G691S and S904S nucleotide changes were in complete linkage disequilibrium, so the results were grouped together and referred to as G691S/S904S haplotype. This haplotype are not considered as oncogenic mutations at this time, its functional role should be investigated. Further analysis is needed to demonstrate the association between this haplotype and MTC development.