Tehran Medical Genetics Laboratory

Tehrān, Iran

Tehran Medical Genetics Laboratory

Tehrān, Iran
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PubMed | Tehran Medical Genetics Laboratory, Tokai University, Hamadan University of Medical Sciences, Shahid Beheshti University of Medical Sciences and University of Strasbourg
Type: Journal Article | Journal: Pharmacogenomics | Year: 2016

This study investigated the influence of HLA class-I and -II genes in the response to IFN- in relapsing-remitting multiple sclerosis (MS) patients.In this cohort, 231 relapsing-remitting MS patients who are classified into IFN- responders (n = 146) and nonresponders (n = 85) and 180 ethnic-matched healthy controls were analyzed. Clinical outcome of IFN- therapy particularly Expanded Disability Status Scale scores were evaluated in relation to HLA-A, -B and -DRB1 alleles and haplotypes.Increased frequencies of HLA-DRB1*04 allele and HLA-A*03-B*44-DRB1*04 haplotype, and decreased frequency of HLA-B*15 were associated with better response to IFN- treatment.The possibility of genetic screening particularly HLA typing prior to starting IFN- therapy for MS may permit the identification of likely responders or nonresponders.

Nezhat N.,Islamic Azad University at Tehran | Akbari M.T.,Tarbiat Modares University | Akbari M.T.,Tehran Medical Genetics Laboratory
Genetic Testing and Molecular Biomarkers | Year: 2012

Although Iran is one of the countries with a high frequency of thalassemia, few studies have been carried out on characterization of different mutations in the α-globin gene cluster. There are a proportion of patients suspected of having α-thalassemia according to hematological profile with no abnormalities identified by gap-PCR for the most common α-thalassemia deletions and no point mutations detected by amplification refractory mutation system and sequencing of the α-globin genes. So the aim of the present study was to identify the mutations at the α-globin cluster using the multiplex ligation-dependent probe amplification (MLPA) method in patients who were suspected to be carrier of α-globin gene mutations, but in whom no mutations were found by conventional techniques. Twenty patients whose mutations were not identified were selected. In addition, 10 and 5 samples were chosen as positive and negative controls, respectively. MLPA results demonstrated mutations in 15% of the cases undetected by the conventional methods. One case showed the deletion of regulatory element HS-40 and in two other cases α-triplication in α-genes was determined. The simplicity and high accuracy of MLPA make this method a complementary method along with gap-PCR for detecting common known and unknown deletions and duplications in the α-globin gene cluster. © Copyright 2012, Mary Ann Liebert, Inc.

Khordadpoor-Deilamani F.,Islamic Azad University at Tehran | Akbari M.T.,Tarbiat Modares University | Akbari M.T.,Tehran Medical Genetics Laboratory | Nafissi S.,Tehran University of Medical Sciences | Zamani G.,Tehran University of Medical Sciences
Genetic Testing and Molecular Biomarkers | Year: 2011

Duchenne's muscular dystrophy and Becker muscular dystrophy (BMD) are X-linked recessive disorders caused by mutations in the dystrophin gene. In this project, 100 unrelated male patients were initially screened for deletions in the dystrophin gene by multiplex polymerase chain reaction, of whom 52 were positive. We performed the multiplex ligation-dependent probe amplification (MLPA) method on 43 of the remaining 48 patients, as well as 12 females suspected to be carriers, to detect deletions and duplications of their dystrophin gene. The MLPA method found deletions and duplications in 8 unidentified male patients. Sequencing revealed that in one case the deletion detected was a point mutation. One of 12 females was heterozygous for deletion of exons 49 and 50. In conclusion, the MLPA method proved to be reliable for studying affected males as well as female carriers. © Copyright 2011, Mary Ann Liebert, Inc.

Khordadpoor-Deilamani F.,Islamic Azad University at Tehran | Akbari M.T.,Tarbiat Modares University | Akbari M.T.,Tehran Medical Genetics Laboratory | Karimipoo M.,Tehran Medical Genetics Laboratory | And 2 more authors.
Molecular Vision | Year: 2015

Purpose: Albinism is a heterogeneous genetic disorder of melanin synthesis that results in hypopigmented eyes (in patients with ocular albinism) or hair, skin, and eyes (in individuals with oculocutaneous albinism). It is associated with decreased visual acuity, nystagmus, strabismus, and photophobia. The tyrosinase gene is known to be involved in both oculocutaneous albinism and autosomal recessive ocular albinism. In this study, we aimed to screen the mutations in the TYR gene in the nonsyndromic OCA and autosomal recessive ocular albinism patients from Iran. Methods: The tyrosinase gene was examined in 23 unrelated patients with autosomal recessive ocular albinism or nonsyndromic OCA using DNA sequencing and bioinformatics analysis. Results: TYR gene mutations were identified in 14 (app. 60%) albinism patients. Conclusions: We found 10 mutations, 3 of which were novel. No mutation was found in our ocular albinism patients, but one of them was heterozygous for the p.R402Q polymorphism. © 2015, Molecular Vision, All rights Reserved.

Asgari N.,Islamic Azad University at Tehran | Akbari M.T.,Tarbiat Modares University | Akbari M.T.,Tehran Medical Genetics Laboratory | Zare S.,Tehran Medical Genetics Laboratory | And 2 more authors.
Journal of Assisted Reproduction and Genetics | Year: 2013

Problem: Numerous lines of evidence implicate Apolipoprotein E (Apo E) in lipid metabolism during pregnancy. Hence, a role for its polymorphism has been envisaged in recurrent pregnancy loss (RPL) considering major structural and functional differences between different Apo E genotypes. Method of study: A case control study of 81 women with two or more pregnancy losses that did not have any other known risk factors including anatomic anomalies of the reproductive system, infections, immunologic factors, hormonal imbalances, chromosomal abnormalities and environmental factors was carried out. The control group consisted of 81 women with at least two healthy children and no RPL in their reproductive history. DNA was extracted from the peripheral blood following written consent and Apo E genotyping was carried out by amplifying exon 4 of the gene and subjecting it to digestion by HhaI restriction enzyme. Results: Genotyping was concluded by analyzing different fragment sizes produced, which resulted in finding significantly higher frequency of combined E3/E4 and E4/E4 genotypes in the patients (about 20 %) compared to the normal controls (2.4 %). The genotypes were confirmed by DNA sequencing. Conclusion: Allelic frequency for E4 was 13.5 % in the patients and only 1 % in the non-RPL group. Our findings confirm and are in line with a number of similar studies carried out on other populations. Therefore, Apo E4 polymorphism seems to be contributing to the thrombophilic risk factors as a background to RPL. © 2012 Springer Science+Business Media New York.

PubMed | Tarbiat Modares University, Tehran Medical Genetics Laboratory and Islamic Azad University at Tehran
Type: Journal Article | Journal: Journal of human genetics | Year: 2016

Albinism is a heterogeneous genetic disorder of melanin synthesis that results in hypopigmented hair, skin and eyes. It is associated with decreased visual acuity, nystagmus, strabismus and photophobia. Six genes are known to be involved in nonsyndromic oculocutaneous albinism (OCA). In this study, we aimed to find the disease causing mutations in albinism patients using homozygosity mapping. Twenty three unrelated patients with nonsyndromic OCA or autosomal recessive ocular albinism were recruited in this study. All of the patients parents had consanguineous marriage and all were screened for TYR mutations previously. At first, we performed homozygosity mapping using fluorescently labeled primers to amplify a novel panel of 13 STR markers inside the OCA genes and then the screened loci in each family were studied using PCR and cycle sequencing methods. We found five mutations including three mutations in OCA2, one mutation in SLC45A2 and one mutation in C10ORF11 genes, all of which were novel. In cases where the disease causing mutations are identical by descent due to a common ancestor, these STR markers can enable us to screen for the responsible genes.

Shakarami F.,Guilan University | Akbari M.T.,Tarbiat Modares University | Akbari M.T.,Tehran Medical Genetics Laboratory | Karizi S.Z.,Islamic Azad University at Varamin
International Journal of Reproductive BioMedicine | Year: 2015

Background: Recurrent pregnancy loss (RPL) defined by two or more failed pregnancies before 20 weeks of gestation. Several factors play a role in RPL including thrombophilic conditions which can be influenced by gene polymorphisms. Plasminogen activator inhibitor-1 (PAI-1) and angiotensin converting enzyme (ACE) genes are closely related to fibrinolytic process, embryonic development and pregnancy success. Objective: The aim of this study was to investigate the relationship between RPL and common polymorphisms in ACE and PAI-1 genes. Materials and Methods: In this case control study, 100 women with recurrent abortions (at least two) were selected as cases and 100 healthy women with two or more normal term deliveries without a history of abortion as controls. Total genomic DNA was isolated from blood leukocytes. The status of the PAI-1 4G/5G and ACE (D/I) polymorphism was determined by PCR-RFLP. Results: Homozygosity for PAI-1 4G polymorphism was seen in 17 cases (17%), and 5 controls (5%) (p=0.006) so patients with homozygote 4G mutation were significantly more prone to RPL in contrast to control group (OR: 4.63, % 95 CI: 1.55-13.84). In addition, 7 patients (7%), and no one from the control group, were homozygote (I/I) for ACE polymorphism (p=0.034), suggesting no significant associations between ACE D allele or DD genotype and RPL. Conclusion: Considering these results, because 4G/4G polymorphism for PAI-1 gene could be a thrombophilic variant leading to abortion, analysis of this mutation and other susceptibility factors are recommended in patients with RPL. © 2015, Research and Clinical Center for Infertitlity. All rights reserved.

Akbari M.T.,Tarbiat Modares University | Akbari M.T.,Tehran Medical Genetics Laboratory | Hamid M.,Pasteur Institute of Iran
Archives of Iranian Medicine | Year: 2012

Background: This study was carried out to identify molecular and hematological features of α- globin chain variants and to evaluate their effects on the clinical and hematological characteristics in Iranian individuals suspected of having thalassemia trait. Methods: Analysis ofred blood cell indices, hemoglobin (Hb) analysis and genomic DNA isolation were carried out according to standard methods. For identifying the a-thalassemia (α-thal) genotype, investigation of common Mediterranean a-globin gene deletions (-α3.7, -α4-2 -α20-5 and -MED) was performed by Gap-PCR. To characterize chain variants the entire α1, and α2 genes that spanned from the promoter region to the poly A tail were amplified and directly sequenced. Results: In this study, 19 members of 17 unrelated families showed a-chain variants. Among these cases ten a-chain variantsthat included Hb Setif, Hb Constant Spring (Hb CS), Hb Handsworth, Hb Icaria, Hb Evanston, Hb Val de Marne, Hb Utrecht, Hb Savaria, Hb Adana, and Hb Dartmouth were identified. The hematological profile and molecular basis of these ten α-chain variants and the phenotypic consequences oftheir interactionswere discussed. Conclusion: The knowledge of the spectrum of α-globin variants present in the Iranian population is essential for the molecular diagnosis and prevention ofhemoglobinopathies.

Hamid M.,Pasteur Institute of Iran | Akbari M.T.,Tarbiat Modares University | Akbari M.T.,Tehran Medical Genetics Laboratory
Medical Principles and Practice | Year: 2011

Objective: To describe hematological and molecular features of a 13-bp deletion in the 3′ untranslated region(3′ UTR) of the β-globin gene in carrier individuals and a compound heterozygous patient. Subjects and Methods: Five members of an Iranian family of Persian ethnic origin were studied. Red blood cell indices and hemoglobin analysis were carried out according to standard methods. Genomic DNA was obtained from peripheral blood cells by salting-out procedures. β-Globin gene amplification and DNA sequencing were performed. Results: One patient had a 13-bp deletion in the 3′ UTR of the β-globin gene that causes the β-thalassemia phenotype in combination with the IVSII-1 (G→A) mutation. The patient had inherited the IVSII-1 (G→A) mutation from his mother, while the second β-globin gene (inherited paternally) had a 13-bp deletion at nucleotide 90 downstream of the termination codon (CD +90 del 13 bp).The patient's father and paternal grandmother, who are carriers of this deletion, had no hematological abnormalities. Conclusion: This case showed a patient with a 13-bp deletion in the 3′ UTR of β-globin gene that could cause a slight decrease in the stability of the mRNA, but did not have a hematological effect in the heterozygotes. The 13-bp deletion could be clinically important only in situations where β-chain synthesis in trans is compromised. Copyright © 2011 S. Karger AG, Basel.

PubMed | Tarbiat Modares University and Tehran Medical Genetics Laboratory
Type: Journal Article | Journal: Iranian journal of public health | Year: 2015

Lamellar ichthyosis is one form of congenital autosomal recessive ichthyosis. To date, seven causative genes for ARCI have been identified. To understand further the genetic spectrum of the disease, we analyzed a four-generation Iranian family with ARCI that had observable inheritance. Exome sequencing data for one of the affected individuals with ichthyosis from a consanguineous Iranian family was analyzed. Potential candidate mutations were analyzed in additional family members to determine if the putative mutation segregated with disease status. A novel homozygous mutation (p.D414V) in TGM1 and rs3027232 in ALOXE3 gene in heterozygous form were identified which segregated with disease status in the family. Bioinformatic studies with Polyphen-2 and SIFT showed that these variants are damaging. We identified a possible triallelic inheritance in this study. Moreover, this paper illustrates how advances in genome sequencing technologies could be utilized to rapidly elucidate the molecular basis of inherited skin diseases which can be caused by mutations in multiple disease genes.

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