Three novel mutations in CYBA among 22 Iranians with Chronic granulomatous disease.

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by defect in one of the components of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase enzyme. The enzyme is at least composed of membrane-bound subunits gp91-phox and p22-phox (also named cytochrome b558 ), and cytosolic ones p40-phox, p47-phox and p67-phox. A defect in the enzyme activity leads to impaired intracellular killing of phagocytic cells. The CYBA gene encoding p22-phox is located on chromosome 16q24. In this study, new genetic changes of CYBA gene in 22 Iranian patients with autosomal recessive-CGD (AR-CGD) were identified. Twenty-two patients with CGD were referred to Immunology, Asthma and Allergy Research Institute (IAARI) and enrolled in this study based on defect in NADPH oxidase activity, demographic data and clinical histories. All patients had p22-phox deficiency based on Western blotting. Genomic DNA was extracted from peripheral blood mononuclear cells (PBMCs), and PCR followed by direct sequencing was performed to find p22-phox mutations. Mutation analysis of CYBA revealed 12 different mutations, including three novel mutations: one was deletion of exon 1, and two were point mutations in exon 3 (c.136G>A (p.Gly46Ser)), and exon 6 (c.388C>T (p.Gln130X)). Three new mutations of CYBA gene in four of 22 Iranian patients with AR-CGD were found. These three novel mutations can partly complete the database of Human Gene Mutation Database (HGMD) and other related ones. It can also be helpful for further prenatal diagnosis in the affected families. Given that currently bone marrow transplantation is considered to be the curative treatment for patients with CGD, finding mutations will also be useful for timely decision-making in bone marrow transplantation.

Increased levels of mitochondrial DNA copy number in patients with vitiligo.

BACKGROUND: Oxidative stress is known to be involved in the pathogenesis of autoimmune diseases such as vitiligo. Evidence suggests that the human mitochondrial DNA copy number (mtDNAcn) is vulnerable to damage mediated by oxidative stress. The purpose of this study was to examine and compare peripheral blood mtDNAcn and oxidative DNA damage byproducts (8-hydroxy-2-deoxyguanosine; 8-OHdG) in patients with vitiligo and healthy controls (HCs). METHODS: The relative mtDNAcn and the oxidative damage (formation of 8-OHdG in mtDNA) of each sample were determined by real-time quantitative PCR. Blood samples were obtained from 56 patients with vitiligo and 46 HCs. RESULTS: The mean mtDNAcn and the degree of mtDNA damage were higher in patients with vitiligo than in HCs. CONCLUSION: These data suggest that increase in mtDNAcn and oxidative DNA damage may be involved in the pathogenesis of vitiligo.

Clinical, Laboratory, and Molecular Findings for 63 Patients With Severe Combined Immunodeficiency: A Decade´s Experience.

BACKGROUND: Severe combined immunodeficiency (SCID) is a life-threatening pediatric disease. We report on the clinical evaluation, immunological assessment, molecular analysis, and outcomes of SCID patients in a tertiary referral center in Iran. METHODS: From January 2006 to December 2015, we performed a prospective cohort study in which initial screening and advanced immunological tests were carried out on patients suspected of having SCID. Genetic analysis was also performed to confirm the diagnosis. RESULTS: A total of 63 patients were diagnosed with SCID (43 male [68.3%]). The median age at onset and diagnosis and diagnostic delay were 40 and 110 and 60 days respectively. A total of 49 patients (77.8%) had a history of BCG vaccination, and of these, one-third experienced BCG-associated complications. The most common clinical manifestations were pneumonia, recurrent oral candidiasis, chronic diarrhea, and failure to thrive. Of the thirteen patients who underwent hematopoietic stem cell transplantation, 8 survived and 5 died before they could receive the transplant. Most patients (34.9%) were classified as having T-B-NK+ SCID and had a mutation in the RAG2 or RAG1 gene. CONCLUSIONS: Autosomal recessive SCID is the most common type in Iranian patients. Providing high-quality training to physicians and patients' families to reduce the diagnostic delay should be prioritized. It is also important to raise awareness of live vaccination and to expand stem cell donor registries to speed up the transplantation process.

Clinical, laboratory, and molecular findings for 63 patients with severe combined immunodeficiency: a decade's experience

Introduction: Severe combined immunodeficiency (SCID) is a life-threatening pediatric disease. We report on the clinical evaluation, immunological assessment, molecular analysis, and outcomes of SCID patients in a tertiary referral center in Iran. Methods: From January 2006 to December 2015, we performed a prospective cohort study in which initial screening and advanced immunological tests were carried out on patients suspected of having SCID. Genetic analysis was also performed to confirm the diagnosis. Results: A total of 63 patients were diagnosed with SCID (43 male [68.3%]). The median age at onset and diagnosis and diagnostic delay were 40 and 110 and 60 days respectively. A total of 49 patients (77.8%) had a history of BCG vaccination, and of these, onethird experienced BCG-associated complications. The most common clinical manifestations were pneumonia, recurrent oral candidiasis, chronic diarrhea, and failure to thrive. Of the thirteen patients who underwent hematopoietic stem cell transplantation, 8 survived and 5 died before they could receive the transplant. Most patients (34.9%) were classified as having T-B-NK+ SCID and had a mutation in the RAG2 or RAG1 gene. Conclusion: Autosomal recessive SCID is the most common type in Iranian patients. Providing high-quality training to physicians and patients’ families to reduce the diagnostic delay should be prioritized. It is also important to raise awareness of live vaccination and to expand stem cell donor registries to speed up the transplantation process (AU)

Introducción: La inmunodeficiencia combinada severa (SCID) es una grave enfermedad pediátrica que puede comprometer la vida del paciente. El artículo recoge la evaluación clínica e inmunológica, el análisis molecular y la supervivencia de los pacientes con SCID atendidos en un hospital de referencia de Irán. Métodos: Desde enero de 2006 a diciembre de 2015, se realizó un estudio prospectivo en los pacientes con SCID en el que se realizó un screening inicial junto a diferentes análisis inmunológicos. Se realizó un análisis genético para confirmar el diagnóstico. Resultados: Sesenta y tres pacientes fueron diagnosticados de SCID, cuarenta y tres (63,8%) de los mismos eran varones. La mediana de la edad de inicio de la enfermedad, diagnóstico y retraso en su diagnóstico, fueron de 40, 110 y 60 días respectivamente. Cuarenta y nueve pacientes (77,8%) recibieron vacunación con BCG y un tercio de los mismos presentó complicaciones como consecuencia de la misma. Las manifestaciones clínicas más frecuentes de estos pacientes fueron: neumonía, candidiasis oral recidivante, diarrea crónica y retraso en el crecimiento. Ocho de los treces pacientes que recibieron trasplante de progenitores hematopoyéticos, lograron sobrevivir. Los restantes pacientes fallecieron antes de poder recibir dicho trasplante. El 34,9% de los pacientes tuvieron T-B-NK+ SCID y la mayoría de los pacientes eran portadores de mutaciones en los genes RAG2 o RAG1. Conclusión: La variante autosómica recesiva de la SCID es la forma más común en los pacientes iraníes. Se debe considerar prioritario proporcionar una formación adecuada a los médicos y las familias para reducir el retraso en el diagnóstico. Es igualmente importante concienciar para evitar la vacunación con gérmenes vivos y expandir los registros de donantes de células madre para agilizar el trasplante de estos pacientes (AU)

[Clinical polymorphisms and approaches of arrhythmias treatment in a family with δKPQ1505-1507 deletion in SCN5A gene].

BACKGROUND: The aim of the study was to analyze spectrum of manifestation and treatment response in large family with rhythm disturbances caused by p.delKPQ1505-1507 mutation in SCN5A gene. PATIENTS AND METHODS: We had under our observation 18 members of large Iranian family with various combination of inherited arrhythmic syndromes. Careful cardiological examination, genetic councelling and venous blood sampling for molecular genetic study were performed for family members. Mutation screening in SCN5A gene was performed using bidirectional Sanger sequencing. RESULTS: Here by we show the observation of Iranian family with known mutation p.delKPQ 1505-1507 in SCN5A gene, who display not only LQ-TS phenotype but also some of the carriers of this mutation have had LQ-TS and Brugada syndrome (combine phenotype), interestingly. CONCLUSION: The overlapping phenotype associated with high risk of sudden cardiac death may require complex approaches to antiarrhythmic therapy, surgical treatment and prevention of sudden cardiac death in the family.

Mitochondrial and nuclear genes as the cause of complex I deficiency.

Multiple sclerosis (MS) is an immunological inflammatory disease of the central nervous system. The pathogenesis of MS is incompletely understood, but various studies have suggested that mitochondrial dysfunction is associated with the disease. Mitochondria are among the main cellular sources of reactive oxygen and nitrogen species, and they play a pivotal role in many neuro-pathological conditions. The mitochondrial nuclear subunit of complex I gene in mitochondria may play a role in MS, and understanding this role may provide rationale for novel approaches to treatment of the disease and the development of novel therapies. We designed a molecular study to demonstrate biochemical defects in complex I activity and found some novel nucleotide substitutions in mitochondrial DNA that might be involved in the pathogenesis of MS. The mitochondrial complex subunit I sequence was amplified and sequenced in MS patients. Although no reported pathogenic mutations were found in these patients, other studies have clearly indicated that the mitochondrial nuclear complex subunit I gene plays a significant role in MS pathogenesis.

Novel Mutations in Sandhoff Disease: A Molecular Analysis among Iranian Cohort of Infantile Patients.

BACKGROUND: Sandhoff disease is an autosomal recessive disorder caused by ß-hexosaminidase deficiency and accumulation of GM2 ganglioside resulting in progressive motor neuron manifestations and death from respiratory failure and infections in infantiles. Pathogenic mutations in HEXB gene were observed which leads to enzyme activity reduction and interruption of normal metabolic cycle of GM2 ganglioside in sandhoff patients. METHODS: Six infantile index patients with typical biochemical and clinical picture of the disease were studied at the molecular level. After DNA extraction and amplification, probands and their parents, were evaluated by direct sequencing of amplicons. RESULTS: We identified 7 different mutations among which 4 were novel. The most prevalent finding (50%) among our population was a 16 kb deletion including the promoter and exons 1-5. The other findings included c.1552delG and c.410G>A, c.362 A>G, c.550delT, c.1597C>T, c.1752delTG. CONCLUSION: We conclude that Cys137Tyr and R533C mutations may be pathogenic because of changing amino acid and locating at the conserved region and also they have not been observed in hundred controls. Besides, four mutations including: Cys137Tyr, c.1552delG, c.1597C>T and c.550delT fulfilled almost criteria for pathogenic mutation.

Effects of prebiotic, protein level, and stocking density on performance, immunity, and stress indicators of broilers.

An experiment was conducted to determine the effects of period on the performance, immunity, and some stress indicators of broilers fed 2 levels of protein and stocked at a normal or high stocking density. Experimental treatments consisted of a 2 × 2 × 2 factorial arrangement with 2 levels of prebiotic (with or without prebiotic), 2 levels of dietary CP [NRC-recommended or low CP level (85% of NRC-recommended level)], and 2 levels of stocking density (10 birds/m(2) as the normal density or 16 birds/m(2) as the high density), for a total of 8 treatments. Each treatment had 5 replicates (cages). Birds were reared in 3-tiered battery cages with wire floors in an open-sided housing system under natural tropical conditions. Housing and general management practices were similar for all treatment groups. Starter and finisher diets in mash form were fed from 1 to 21 d and 22 to 42 d of age, respectively. Supplementation with a prebiotic had no significant effect on performance, immunity, and stress indicators (blood glucose, cholesterol, corticosterone, and heterophil:lymphocyte ratio). Protein level significantly influenced broiler performance but did not affect immunity or stress indicators (except for cholesterol level). The normal stocking density resulted in better FCR and also higher antibody titer against Newcastle disease compared with the high stocking density. However, density had no significant effect on blood levels of glucose, cholesterol, corticosterone, and the heterophil:lymphocyte ratio. Significant interactions between protein level and stocking density were observed for BW gain and final BW. The results indicated that, under the conditions of this experiment, dietary addition of a prebiotic had no significant effect on the performance, immunity, and stress indicators of broilers.

Effects of non-antibiotic feed additives on performance, tibial dyschondroplasia incidence and tibia characteristics of broilers fed low-calcium diets.

This experiment was conducted to investigate and compare the efficacy of different feed additives on performance, tibial dyschondroplasia (TD) incidence and tibia characteristics of male broilers fed low-calcium diets. A completely randomized design, with six treatments and five replicates of five chicks per each was used. Experimental treatments were: (i) Basal diet containing recommended level of calcium (0.9%) as control treatment (Ctrl), (ii) low-calcium (0.67%) diet without any additive (LC), (iii) low-calcium diet + probiotic (2 g/kg diet), (iv) low-calcium diet + prebiotic (2 g/kg diet), (v) low-calcium diet + synbiotic [mix of probiotic and prebiotic (each 2 g/kg diet)], (vi) low-calcium diet + organic acid (1.5 g/kg diet). Birds were reared in an open-sided house system under natural tropical condition until 21 days of age. Feeding with low-calcium diet negatively influenced broiler performance (body weight, body weight gain and feed conversion ratio) and tibia characteristics, whereas dietary inclusion of all feed additives had beneficial effects on above-mentioned parameters and helped the birds to overcome problems related to low-calcium diets. Different treatments had no effect on TD incidence.

Leber hereditary optic neuropathy: do folate pathway gene alterations influence the expression of mitochondrial DNA mutation?

BACKGROUND: Leber hereditary optic neuropathy (LHON) is an inherited form of bilateral optic atrophy leading to the loss of central vision. The primary cause of vision loss is mutation in the mitochondrial DNA (mtDNA), however, unknown secondary genetic and/or epigenetic risk factors are suggested to influence its neuropathology. In this study folate gene polymorphisms were examined as a possible LHON secondary genetic risk factor in Iranian patients. METHODS: Common polymorphisms in the MTHFR (C677T and A1298C) and MTRR (A66G) genes were tested in 21 LHON patients and 150 normal controls. RESULTS: Strong associations were observed between the LHON syndrome and C677T (P= 0.00) and A66G (P= 0.00) polymorphisms. However, no significant association was found between A1298C (P =0.69) and the LHON syndrome. CONCLUSION: This is the first study that shows MTHFR C677T and MTRR A66G polymorphisms play a role in the etiology of the LHON syndrome. This finding may help in the better understanding of mechanisms involved in neural degeneration and vision loss by LHON and hence the better treatment of patients.

Plasma glucose lowering effect of the wild Satureja khuzestanica Jamzad essential oil in diabetic rats: role of decreased gluconeogenesis.

This study was to evaluate the effect of the wild SKEO on activities and genes expression of hepatic Glycogen Phosphorylase (GP) and phosphoenolpyruvate carboxykinase (PEPCK) in normal and diabetic rats. The wild SKEO was orally administered at different doses (50 and 100 mg/kg/day) to normal as well as diabetic rats for 21 days. The levels of mRNA were determined using the quantitative real-time RT-PCR technique. The plasma glucose concentrations of diabetic rats receiving SKEO (100 mg kg(-1)) compared with diabetic control were significantly decreased. Hepatic GP activity and its mRNA levels of diabetic rats treated with SKEO moderately increased. The activity of hepatic PEPCK and its mRNA levels were significantly decreased in normal rats treated with SKEO (100 mg kg(-1)). The enhancement of PEPCK activity and its mRNA levels of diabetic treated rats with SEKO (100 mg kg(-1)) was significantly decreased compared with diabetic control. In conclusion, an excessive inhibition of PEPCK in liver of diabetic rats treated with the wild SKEO may contribute to the plasma glucose lowering action of SKEO that seems to be in relation with antioxidant properties of SKEO.

Application of multiplex PCR with histopathologic features for detection of familial breast cancer in formalin-fixed, paraffin-embedded histologic specimens.

Breast cancer is the most common malignancy among females in the world. Age and familial history are the major risk factors for the development of this disease in Iran. Mutations of BRCA1 and BRCA2 genes are associated with a greatly increased risk for development of familial breast cancer. Frequency of BRCA mutations was identified in familial breast cancers (FBC) and non-familial breast cancers (NFBC) by molecular genetics, morphological and Immunohistochemical methods. Thirty forth formalin-fixed, paraffin-embedded breast tissue tumors were analyzed from 16 patients with FBC and 18 patients with NFBC. Three 5382insC mutations detected by multiplex PCR in 16 familial breast cancers. Immunohistochemical method was used to detect estrogen receptor (ER) and progesterona receptor (PR) and TP53. Comparison of ER, PR and TP53 exhibited high difference (P < 0.0001) in familial breast cancers and non-familial breast cancers. Our results demonstrated that 5382insC mutation, ER, PR, TP53, mitotic activity, polymorphism, necrosis and tubules can serve as the major risk factors for the development of FBC.

The first study of galactose-1-phosphate uridyl transferase mutations in Iranian galactosemia patients.

OBJECTIVES: Classical galactosemia (McKusick 230400) is an autosomal recessive disorder caused by mutations in the galactose-1-phosphate uridyl transferase (GALT;EC 2.7.7.10) gene. DESIGN AND METHODS: In the present study, we report molecular analysis of 14 unrelated Iranian galactosemia children with reduced or without GALT activity using PCR-RFLP and SSCP-Sequencing methods. RESULTS: Q188R mutation was the most observed mutation with the allelic frequency of 57.1%. The allelic frequencies for S135L, Y209S, A320T, and K285N were found to be 7.1%, 7.1%, 7.1%, and 3.57% respectively. CONCLUSIONS: Our results show that galactosemia is a heterogeneous disorder at the molecular level among the Iranian population.

Identification of a new human mtDNA polymorphism (A14290G) in the NADH dehydrogenase subunit 6 gene.

Leber's hereditary optic neuropathy (LHON) is a maternally inherited form of retinal ganglion cell degeneration leading to optic atrophy in young adults. Several mutations in different genes can cause LHON (heterogeneity). The ND6 gene is one of the mitochondrial genes that encodes subunit 6 of complex I of the respiratory chain. This gene is a hot spot gene. Fourteen Persian LHON patients were analyzed with single-strand conformational polymorphism and DNA sequencing techniques. None of these patients had four primary mutations, G3460A, G11788A, T14484C, and G14459A, related to this disease. We identified twelve nucleotide substitutions, G13702C, T13879C, T14110C, C14167T, G14199T, A14233G, G14272C, A14290G, G14365C, G14368C, T14766C, and T14798C. Eleven of twelve nucleotide substitutions had already been reported as polymorphism. One of the nucleotide substitutions (A14290G) has not been reported. The A14290G nucleotide substitution does not change its amino acid (glutamic acid). We looked for base conservation using DNA star software (MEGALIGN program) as a criterion for pathogenic or nonpathogenic nucleotide substitution in A14290G. The results of ND6 gene alignment in humans and in other species (mouse, cow, elegans worm, and Neurospora crassa mold) revealed that the 14290th base was not conserved. Fifty normal controls were also investigated for this polymorphism in the Iranian population and two had A14290G polymorphism (4%). This study provides evidence that the mtDNA A14290G allele is a new nonpathogenic polymorphism. We suggest follow-up studies regarding this polymorphism in different populations.

Identification of a new human mtDNA polymorphism (A14290G) in the NADH dehydrogenase subunit 6 gene

Leber's hereditary optic neuropathy (LHON) is a maternally inherited form of retinal ganglion cell degeneration leading to optic atrophy in young adults. Several mutations in different genes can cause LHON (heterogeneity). The ND6 gene is one of the mitochondrial genes that encodes subunit 6 of complex I of the respiratory chain. This gene is a hot spot gene. Fourteen Persian LHON patients were analyzed with single-strand conformational polymorphism and DNA sequencing techniques. None of these patients had four primary mutations, G3460A, G11788A, T14484C, and G14459A, related to this disease. We identified twelve nucleotide substitutions, G13702C, T13879C, T14110C, C14167T, G14199T, A14233G, G14272C, A14290G, G14365C, G14368C, T14766C, and T14798C. Eleven of twelve nucleotide substitutions had already been reported as polymorphism. One of the nucleotide substitutions (A14290G) has not been reported. The A14290G nucleotide substitution does not change its amino acid (glutamic acid). We looked for base conservation using DNA star software (MEGALIGN program) as a criterion for pathogenic or nonpathogenic nucleotide substitution in A14290G. The results of ND6 gene alignment in humans and in other species (mouse, cow, elegans worm, and Neurospora crassa mold) revealed that the 14290th base was not conserved. Fifty normal controls were also investigated for this polymorphism in the Iranian population and two had A14290G polymorphism (4 percent). This study provides evidence that the mtDNA A14290G allele is a new nonpathogenic polymorphism. We suggest follow-up studies regarding this polymorphism in different populations.

Lack of association between interferon-gamma receptor-1 polymorphism and pulmonary TB in Iranian population sample.

BACKGROUND: Tuberculosis is one of the most common infectious diseases in the world. In recent years, genetically approach has been developed. One of the interesting gene for investigator is IFN-gammaR1. AIM: Determination of susceptibility to tuberculosis with polymorphism of IFN-gammaR1 gene. MATERIAL AND METHOD: Study was prospective case-control. Fifty patients with smear positive tuberculosis have been chosen randomly. They were matched with 54 healthy controls with no history of TB. Polymorphism at 395 codon of IFN-gammaR1 gene was detected with Newport method. Data were analysed with SPSS version 11. RESULTS: Mean age of patients and control were 55+/-20 and 53+/-13.5 years, respectively. Demographic characteristic had no difference within two groups. One patient in case group had heterozygote mutation at IFN-gammaR1 gene. In control group there were no mutations. CONCLUSION: Genetically susceptibility to TB is not in 395 colon of IFN-gammaR1 in Iranian TB sample and polymorphism of this loci has occur in 2% of TB patients and 0.96% of total study population.

Population screening for association of mitochondrial haplogroups BM, J, K and M with multiple sclerosis: interrelation between haplogroup J and MS in Persian patients.

BACKGROUND: Multiple sclerosis (MS) is an immunological inflammatory disease of the central nervous system (CNS) which is chronically observed in young adults. On the basis of earlier studies, potential relatedness between MS and mitochondrial DNA (mtDNA) mutations was postulated. MATERIALS AND METHODS: 246 individuals were screened using the PCR-RFLP method, including 70 MS patients examined for mitochondrial haplogroups BM, J, K and M and 176, 149 and 70 normal controls examined for haplogroups BM and M, J and K, respectively. RESULTS AND DISCUSSION: Our analysis revealed a relatively high proportion of haplogroup BM in MS patients (approximately 26%) compared to normal controls ( approximately 13%). In addition, a slightly significant increase of MS patients of haplogroup J (20% in MS patients versus 9.39% in normal controls at P =0.049), while haplogroups M and K did not show contribution to MS contingency (2.85 and 2.27%, respectively at P = 1.000 in haplogroup M and 12.85 and 7.14% respectively at P =0.399 in haplogroup K).

Effect of aerobic exercise training on mtDNA deletion in soleus muscle of trained and untrained Wistar rats.

BACKGROUND: According to the theory of mitochondrial aging, oxidative stress plays a major role in aging and age related degenerative diseases. Since oxygen consumption and reactive oxygen species rate increase during aerobic exercise, we hypothesised that heavy aerobic training could lead to enhanced mitochondrial DNA (mtDNA) deletion in postmitotic tissues, leading in turn to premature aging and degenerative diseases. METHODS: Sixty adult male 2 month old Wistar14848 rats were divided into six equal groups. Two groups were trained for 3 months by running on a treadmill (5 days/week, incline 6 degrees; group 1: 40 m/min, 20 min/day; group 2: 20 m/min, 40 min/day), while two sedentary groups participated in aerobic exercise only at the end of the study (incline 6 degrees; group 3: 40 m/min; group 4: 20 m/min). To control for physical and physiological parameters, two groups of untrained animals were killed at the beginning (group 6) and end (group 5) of the study. Expand long PCR was used to investigate mtDNA deletion in soleus muscle and a sequencing method was used to confirm the mtDNA deletion break point. RESULTS: Our results did not show any mtDNA deletion in untrained rats or in those that underwent moderate training (group 2) We only found mtDNA deletion (4.6 kb) in the soleus muscle of heavily trained rats (group 1). CONCLUSIONS: These results demonstrate that one session of aerobic exercise does not cause mtDNA deletion in skeletal muscle. The difference in results between heavy and moderate aerobic training may be due to low work rate or up-regulation of inducible antioxidant systems in moderate training.

First study of CF mutations in the CFTR gene of Iranian patients: detection of DeltaF508, G542X, W1282X, A120T, R117H, and R347H mutations.

Thirty-seven unrelated Iranian CF families were screened for the presence of seven common mutations (DeltaF508, G542X, W1282X, G551D, N1303K, 1717-1G-->A, and 621-1G-->T) using ARMS PCR and exons 4 and 7 of the CFTR gene by SSCP method. This study resulted in the identification of 26.8 per cent of all CF alleles: DeltaF508 (16.2 per cent), W1282X (4 per cent), G542X (2.7 per cent), R117H (1.3 per cent), R347H (1.3 per cent), and A120T (1.3 per cent) mutations were detected. To the best of our knowledge, it is the first report of an Asian subject carrying the A120T mutation. Our findings suggest heterogeneity in the Iranian population, stressing the need to draw attention to sequence analysis in order to find population-specific mutations.

Leber's hereditary optic neuropathy: the spectrum of mitochondrial DNA mutations in Iranian patients.

We studied 14 patients with Leber's hereditary optic neuropathy (LHON) to investigate the mtDNA haplotypes associated with the primary mutation(s). Eleven patients carried the mitochondrial DNA (mtDNA) G11778A mutation, while one had the T14484C mutation; one patient had the G3460A mutation and one the G14459A mutation. The Iranian G11778A LHON mutation was not associated with two mtDNA haplogroups-M (0.0% compared with 3.2% in healthy controls) and J (7.7% compared with 10% in healthy controls). Our results showed a similarity in the pattern of LHON primary point mutations between Iranian families with LHON and those of Russian, European, and North American origin. Our results also do not support an association between mtDNA haplogroups J and M with LHON primary point mutations.