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Background and Aims: Epilepsy as a common chronic neurological disorder is characterized by recurrent unprovoked seizures. Febrile seizures are the most common type of epilepsy in infants and children. Our aim was the molecular analysis of SCN1A gene in affected Iranian patients with GEFS+ and Dravet syndrome diagnosed clinically to explain genotype-phenotype correlation and exact classification., Methods: The 34 unrelated Iranian families with epilepsy were selected and screened for SCN1A mutations by MLPA, ARMS, and PCR-RFLP confirmed by direct sequencing., Results: MLPA analysis showed normal patterns, but direct sequencing revealed that generally 20/34 (0.588) probands have common reported single nucleotide polymorphisms (SNPs) (p.A1067G; rs2298771) with allelic frequency as 0.706/0.294 in patients and 0.515/0.485 in control group, respectively, for A/G. No significant differences between groups were observed. Moreover, four novel allelic variants as missense substitutions included two new sequence variation (p.F412 I, p.Y1274N) and two previously reported mutations (p.R101G, p.S103G) that were detected in 4/34 probands but not in control groups and other healthy normal family members., Conclusions: Clinical diagnosis could nearly establish the classification, but mutation screening helps clinicians to confirm their data. We found mutation in four probands and confirmed the net diagnosis. Our data suggest that the clinical symptom variations could be also explained, considering the role of modifier genes such as mitochondrial mutations or other genes responsible for drug metabolism pathways including multiple drug resistance family genes (ABCB1) or MTHFR., (Copyright 2010. Published by Elsevier Inc.)

Ataxia telangiectasia (AT) is an autosomal recessive disorder with an estimated prevalence of 1/40,000 to 1/100,000 in reported populations. There is a 25% possibility for having an affected child when parents are carriers for the ATM gene mutation. There is no cure available for this disease and prenatal testing is strongly recommended for prevention of this disease. Although the preferred method is the direct mutation analysis of the ATM gene, the large size of the ATM gene with 63 exons and the large number of possible mutations in patients considerably limit efficiency of mutation analysis as a diagnostic choice. Indirect method is a better tool when parents are not carriers of founder mutation and pass different mutations to their children. Indirect molecular diagnosis using ATM-related molecular markers facilitates prenatal diagnosis of AT children. In this study, four molecular markers: D11S2179, D11S1787, D11S535, D11S1343 are genotyped in 19 unrelated families from different regions of Iran. Those markers are amplified using extracted sequence primers from the Gene Bank with their described PCR conditions. Amplified products were separated using denaturing PAGE gels, and data were analyzed to detect their pattern of inheritance in each family. In all families, segregation of alleles was according to Mendelian inheritance, and affected chromosomes were distinguishable from unaffected ones. All carriers and affected patients were diagnosed accurately. Thus, this method is effectively useful in prenatal diagnosis of AT.

Background: Leber hereditary optic neuropathy (LHON) is a maternally inherited form of retinal ganglion cell degeneration leading to optic atrophy in young adults. It is caused by three primary point mutations including G11778A, G3460A, and T14484C in the mitochondrial genome. These three mutations account for the majority of LHON cases and affect genes that encode for different subunits of mitochondrial complex I. Mitochondrial DNA (mtDNA) has a non-coding region at the displacement loop (D-loop) that contains two hypervariable segments (HVS-I and HVS-II) with high polymorphism., Methods: To investigate any possible association between LHON primary mutations and mtDNA haplogroups (hg), the nucleotide sequence of the HVS-I region of mtDNA was determined in 30 unrelated Iranian patients with LHON harboring one of the primary mutations and 100 normal controls with the same ethnicity. DNA was extracted from the peripheral blood after having obtained informed consent. The nucleotide sequence of HVS-I (np 16,024-16,383) was directly determined., Results: Our analysis revealed a relatively high proportion of haplogroup J in LHON patients (53.3%) compared to normal controls (20%). In addition, a slightly significant increase of normal controls of haplogroup L has been confirmed (14% in normal controls vs. 0% in LHON patients at p = 0.03), whereas other haplogroups did not show contribution to LHON contingency., Conclusions: The analysis presented here provides evidence that there is an association between G11778A and G3460A with haplogroup J (including J1 and J2) and W, respectively. Therefore, we hypothesize that mtDNA haplogroups J (J1 and J2) and W might act as predisposing haplotypes, increasing penetrance of LHON disease.

Background: The aim of the study was to clarify the role of deletion of mitochondrial DNA (mtDNA) in gastric carcinogenesis and to determine prevalence of mitochondrial deletions in different regions of tumoral tissue in comparison with adjacent non-tumoral tissue in gastric cancer., Methods: In order to investigate whether a high incidence of mutations exists in mtDNA of gastric cancer tissues, we screened five regions of the mitochondrial genome by PCR amplification, Southern blot and DNA sequence analysis., Results: Of 71 cancer patients, the approximately 8.9 kb deletion was detected among different deletions in 9 cases (12.67%) of the tumoral tissues and 1 case (1.40%) in non-tumoral tissues that were adjacent to the tumors. Level of the 8.9 kb deletion has been found to be more than other deletions in tumoral tissues., Conclusions: The approximately 8.9 kb deletion has an obvious correlation with age and histological type. These data suggest that the approximately 8.9 kb deletion in mtDNA may play an important role in gastric carcinogenesis.

Background: The aim of this study was to determine the frequency of delta mtDNA4977 in tumoral cells as compared with adjacent normal cells in gastric cancer., Methods: In order to investigate whether a high incidence of mutation exists in mitochondrial DNA of gastric cancer tissues, we screened one of common region of the mitochondrial genome by PCR amplification and Southern blot followed by DNA sequence analysis. DNA isolated from these cells was used to amplify hypervariable regions ATPase8/6, COXIII, ND3, ND4 and ND5 of delta mtDNA4977., Results: In 107 cancer patients, delta mtDNA4977 was detected in 6 cases (5.60%) of the tumoral tissues and 18 cases (16.82%) of the non-tumoral tissues that were adjacent to the tumors. Levels of delta mtDNA4977 deletions were found to be more in non-tumoral tissues than in adjacent tumoral tissues. There was no correlation of patients with certain clinical parameters like age, sex, tumor location and tumor size; however, there was an obvious relationship with intestinal-type of gastric cancer., Conclusions: Unknown genetic aspects, ambiguous environmental factors and reactive oxygen species (ROS) can cause the delta mtDNA4977 mutation rate to be increased in gastric cancer. The results suggest that percentage level of delta mtDNA4977 is less common and intolerable in tumoral tissue, probably because of high metabolism and ROS generation. We supposed that the cells initially had delta mtDNA4977 transform to tumoral cells and the existed deletion conferred metabolic disadvantage; thus, cells containing such a mtDNA deletion would be overgrown by other cancer cells without this mtDNA deletion. As a result, the presence of delta mtDNA4977 will be low in tumoral cells.