Prevalence of the CYP2D6*10 (C100T), *4 (G1846A), and *14 (G1758A) alleles among Iranians of different ethnicities.

The presence of polymorphisms in the CYP2D6 gene may modulate enzyme level and activity, thereby affecting individual responses to pharmacological treatment. Here, we compared the prevalence of the CYP2D6*10, *4, and 14* alleles in an Iranian population of different ethnicities with those of other populations. Allele and genotype frequency distributions of CYP2D6*10 variants and predicted phenotypes including extensive metabolizers, intermediate metabolizers, and poor metabolizers were analysed in blood samples of 300 unrelated healthy individuals in an Iranian population using polymerase chain reaction (PCR)-restriction fragment length polymorphism, PCR-single-strand conformation polymorphism, and direct genomic DNA sequencing.

Four novel p.N385K, p.V36A, c.1033-1034insT and c.1417-1418delCT mutations in the sphingomyelin Phosphodiesterase 1 (SMPD1) gene in patients with types A and B Niemann-Pick disease (NPD).

Background: Types A and B Niemann-Pick disease (NPD) are autosomal-recessive lysosomal storage disorders caused by the deficient activity of acid sphingomyelinase due to mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene.

Methods: In order to determine the prevalence and distribution of SMPD1 gene mutations, the genomic DNA of 15 unrelated Iranian patients with types A and B NPD was examined using PCR, DNA sequencing and bioinformatics analysis.

Results: Of 8 patients with the p.

Serum miR-125a-5p, miR-145 and miR-146a as diagnostic biomarkers in non-small cell lung cancer.

Background: Lung cancer is becoming the leading cause of cancer-related deaths with high mortality worldwide and in China as well. Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer accounting for approximately 85% of all cases. Over 70% of cases are at loco-regionally advanced stages or have distant metastasis at the time of presentation with subsequently poor prognosis.

Association of genetic variations in the mitochondrial D-loop with β-thalassemia.

Beta-thalassemia, one of the most common single-gene disorders, is the result of reduced or absent production of β-globin chains. Patients with β-thalassemia show weak genotype-phenotype correlations. Mitochondrial DNA polymorphisms are a potential source for different physiological and pathological characteristics and have been found to be associated as genetic modifiers with various pathophysiologies, including cancers and neurodegenerative diseases.

Two novel tyrosinase (TYR) gene mutations with pathogenic impact on oculocutaneous albinism type 1 (OCA1).

Oculocutaneous albinism (OCA) is a heterogeneous group of autosomal recessive disorders resulting from mutations of the tyrosinase (TYR) gene and presents with either complete or partial absence of pigment in the skin, hair and eyes due to a defect in an enzyme involved in the production of melanin. In this study, mutations in the TYR gene of 30 unrelated Iranian OCA1 patients and 100 healthy individuals were examined using PCR-sequencing. Additionally, in order to predict the possible effects of new mutations on the structure and function of tyrosinase, these mutations were analyzed by SIFT, PolyPhen and I-Mutant 2 software.

Effects of simulated microgravity by RCCS on the biological features of Candida albicans.

During the spaceflight, a wide variety of microorganisms may be carried to the outer space by astronauts and aviation component. The yeast Candida albicans is an important opportunistic pathogen responsible for a variety of cutaneous and systemic human infections in human body, and the yeast cell itself could be affected by various stressful environmental factors including the weightless environment. We evaluated the effects of simulated microgravity on biological features of Candida albicans using the rotary cell culture system (RCCS).

New mutation of pelizaeus--merzbacher-like disease; a report from iran.

Pelizaeus--Merzbacher-like disease (PMLD) is a hypomyelinating leukoencephalopathy disorder with a genetically heterogeneous pattern. Mutations in the GJA12/GJC2 gene cause one form of autosomal recessive Pelizaeus--Merzbacher-like disease. Here, we report a new mutation in a -10-month-old girl with nystagmus, psychomotor delay, hypotonicity, head nodding and dysmyelination from healthy second cousin parents.

A newly identified c.1824_1828dupATACG mutation in exon 13 of the GAA gene in infantile-onset glycogen storage disease type II (Pompe disease).

Pompe disease or glycogen storage disease type II is a glycogen storage disorder associated with malfunction of the acid α-glucosidase enzyme (GAA; EC.3.2.

Gene expression profiling of mitochondrial oxidative phosphorylation (OXPHOS) complex I in Friedreich ataxia (FRDA) patients.

Friedreich ataxia (FRDA) is the most frequent progressive autosomal recessive disorder associated with unstable expansion of GAA trinucleotide repeats in the first intron of the FXN gene, which encodes for the mitochondrial frataxin protein. The number of repeats correlates with disease severity, where impaired transcription of the FXN gene results in reduced expression of the frataxin protein. Gene expression studies provide insights into disease pathogenicity and identify potential biomarkers, an important goal of translational research in neurodegenerative diseases.

Detection of intragenic SMN1 mutations in spinal muscular atrophy patients with a single copy of SMN1.

Proximal spinal muscular atrophy is an autosomal recessive disorder characterized by symmetrical muscle weakness due to degeneration of alpha motor neurons in the spinal cord. Homozygous deletions in the SMN1 have been reported in more than 90% of spinal muscular atrophy cases. Compound heterozygous patients account for approximately 4% of spinal muscular atrophy cases.

Three novel mutations in Iranian patients with Tay-Sachs disease.

Background: Tay-Sachs disease (TSD), or GM2 gangliosidosis, is a lethal autosomal recessive neurodegenerative disorder, which is caused by a deficiency of beta-hexosaminidase A (HEXA), resulting in lysosomal accumulation of GM2 ganglioside. The aim of this study was to identify the TSD-causing mutations in an Iranian population.

Methods: In this study, we examined 31 patients for TSD-causing mutations using PCR, followed by restriction enzyme digestion.

Alexander Disease: Report of Two Unrelated Infantile Form Cases, Identified by GFAP Mutation Analysis and Review of Literature; The First Report from Iran.

Background: Alexander disease (AD) is a sporadic leukodystrophy that predominantly affects infants and children and usually results in death within ten years after onset. The infantile form comprises the most of affected individuals. It presents in the first two years of life, typically with progressive psychomotor retardation with loss of developmental milestones, megalencephaly and frontal bossing, seizures, pyramidal signs and ataxia.

Molecular and clinical investigation of Iranian patients with Friedreich ataxia.

Background: Friedreich ataxia (FRDA) is an autosomal recessive disorder caused by guanine-adenine-adenine (GAA) triplet expansions in the FXN gene. Its product, frataxin, which severely reduces in FRDA patients, leads to oxidative damage in mitochondria. The purpose of this study was to evaluate the triple nucleotide repeated expansions in Iranian FRDA patients and to elucidate distinguishable FRDA clinical differences in these patients.

A novel mutation in the aprataxin (APTX) gene in an Iranian individual suffering early-onset ataxia with oculomotor apraxia type 1(AOA1) disease.

Background: Ataxia with oculomotor apraxia type 1 (AOA1) shows early onset with autosomal recessive inheritance and is caused by a mutation in the aprataxin (APTX) gene encoding for the APTX protein.

Methods: In this study, a 7-year-old girl born of a first-cousin consanguineous marriage was described with early-onset progressive ataxia and AOA, with increased cholesterol concentration and decreased albumin concentration in serum. PCR and direct DNA sequencing was performed after DNA extraction.

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

Background: Sandhoff disease is an autosomal recessive disorder caused by β-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.

Identification of a novel arylsulfatase B gene mutation in three unrelated Iranian mucopolysaccharidosis type-VI patients with different phenotype severity.

Background: Mucopolysaccharidosis type-VI (MPS-VI), which is inherited as an autosomal recessive trait, results from the deficiency of N-acetylgalactosamine 4-sulfatase (arylsulfatase B) activity and the lysosomal accumulation of dermatan sulfate. In this study, ARSB mutation analysis was performed on three unrelated patients who were originally from the West Azerbaijan province of Iran.

Methods: After PCR and direct DNA sequencing, DNA extraction was performed.

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.

Gemcitabine/5-flourouracil/leucovorin for the treatment of advanced pancreatic carcinoma.

Background And Objective: The response rate and median survival with gemcitabine monotherapy, although considered the standard treatment for inoperable and metastatic pancreatic cancer, is relatively poor. We tested the efficacy and toxicity of a chemotherapy protocol consisting of gemcitabine, 5-fluorouracil (5-FU) and leucovorin in patients with inoperable or metastatic pancreatic cancer, which was shown to improve median survival in a small phase II trial.

Patients And Methods: Patients older than 18 years of age with histologically or cytologically confirmed adenocarcinoma of the pancreas and bidimensionally measurable disease, and who were chemotherapy- and radiotherapy-naïve, were treated with a chemotherapy protocol consisting of gemcitabine 1250 mg/m2 on day 1, 5-FU 450 mg/m2 and leucovorin 100 mg/m2 on days 1-3.