Identification and characterization of a novel recessive KCNQ1 mutation associated with Romano-Ward Long-QT syndrome in two Iranian families.

BACKGROUND: One of the foremost causes of sudden cardiac death in the young is an inherent cardiac arrhythmia known as Long-QT syndrome (LQTS). Whereas heterozygous mutations typically lead to the Romano-Ward type of LQTS, We have provided a further evidence for the recessive transmission of a novel KCNQ1 gene mutation in two consanguineous families for the first time in Iran. METHODS: Next generation sequencing, DNA Sanger sequencing and haplotype analysis were performed for genotype determination. Twelve different in silico tools were used for predicting the variant pathogenecity along with the family and population study. RESULTS: A novel recessive KCNQ1 variant (p.D564G) was revealed in none of the unrelated healthy individuals but four patients in two apparently unrelated families. The variant was classified as a likely pathogenic mutation by combining the resulted criteria for the changed amino acid. CONCLUSIONS: Identification of the novel mutation not only supports the genetic testing as a definitive diagnostic tool for detection of at risk family members, but also emphasizes its screening in Iranian LQTS patients as this mutation is very likely a founder mutation in Iran.

The prevalence of common CFTR mutations in Iranian infertile men with non-CAVD obstructive azoospermia by using ARMS PCR techniques.

PURPOSE: To evaluate five common cystic fibrosis trans-membrane conductance regulator (CFTR) mutations (ΔF508, G542X, R117H, W1282X and N1303K) in the Iranian infertile men with noncongenital absence of vas deferens (CAVD) obstructive azoospermia. METHODS: The common CFTR gene mutations were tested on blood samples from 53 infertile men with non-CAVD obstructive azoospermia and 50 normal men as control individuals. Genomic DNA is extracted from the whole blood and the common CFTR mutations have been detected by the amplification refractory mutation system (ARMS) techniques. RESULTS: The common CFTR mutations were found positive in 5/53)9.43%(for ΔF508 and 4/53)7.55%(for G542X mutation of all patients tested. Also, no CFTR mutations were detected in the normal men. CONCLUSION: The common CFTR mutations were detected in 9/53(17%) infertile men with non-CAVD obstructive azoospermia. Pre-treatment CFTR mutation analysis remains critical to distinguish cystic fibrosis (CF) genotypes for men with non CAVD obstructive azoospermia.

Beta-thalassemia intermedia from southern Iran: IVS-II-1 (G-->A) is the prevalent thalassemia intermedia allele.

The preliminary results of a pilot study are reported, intended as an initiation of a research plan, focused on the prevention of beta-thalassemia in Iran. The aims of this study are: (i) to improve the knowledge of the molecular background of beta-thalassemia intermedia in Southern Iran; (ii) to verify the role of the -158 (G)gamma (C-->T) (Xmn I) polymorphism as a modulating factor in thalassemia intermedia; (iii) to test the validity of the multiplex and single mutation specific amplification refractory mutation system in analyzing the molecular defects causing beta-thalassemia in multiethnic populations; and (iv) to develop suitable strategies for the application of prevention protocols in Iran. To accomplish the task we have selected 87 beta-thalassemia intermedia patients and adapted the DNA methodology to detect the following 11 frequent mutations in Iran: codon 5 (-CT); frameshift codons (FSC) 8/9 (+G); codon 30 (G-->C); IVS-I-1 (G-->A); IVS-I-5 (G-->C); IVS-I-6 (T-->C); IVS-I-110 (G-->A); codons 36/37 (-T); codon 44 (-C); IVS-II-1 (G-->A); IVS-II-745 (C-->G). Because of the multiethnicity of the population we have also included the Indian IVS-I (25 bp deletion) and the Mediterranean IVS-I-130 (G-->C) and codon 39 (C-->T) mutations. Forty-eight patients were randomly studied for the Xmn I polymorphism together with 50 healthy volunteers as a control group. The molecular analysis conducted in Iran, identified only 31% of the alleles that were presumed to be thalassemic, revealing either a strategic or a technical insufficiency of the chosen method. However, the mutations with the highest prevalence in the country (IVS-II-1, IVS-I-110, IVS-I-1 and FSC 8/9) were found. As expected the IVS-II-1 defect, being the most frequent in south Iran, was present at the highest rate (24%). The Xmn I polymorphism was found in association with this prevalent mutation and was detected in the homozygous state in 87.5% of the patients homozygous for the IVS-II-1 (G-->A) mutation. The overall positivity for Xmn I was found in 40.6% of the thalassemic alleles vs. 14% in the non-thalassemic, confirming the hypothesis of an older event, antecedent to the IVS-II-1 mutation. In trying to assess a more suitable molecular detection method we intend to continue this study in collaboration with the European centers involved, applying more effective technologies and better defining the molecular spectrum of beta-thalassemia in the sub-populations. We also intend to verify the effect of alpha-thalassemia in the genotype/phenotype correlation of beta-thalassemia intermedia.