Sirous Zeinali

Publications (25) View all

• Article: BRCA1 and BRCA2 germline mutations in 85 Iranian breast cancer patients.

  Fatemeh Keshavarzi, Gholam Reza Javadi, Sirous Zeinali
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  ABSTRACT: Breast cancer is the most common cancer in Iranian women (Mousavi et al in Asian Pac J Cancer Prev 9(2):275-278, 2008). Genetic predisposition accounts for 15% of all breast cancers and germline mutations in breast cancer susceptibility genes, BRCA1 and BRCA2 are responsible for a substantial proportion of high-risk breast and breast/ovarian cancer families (Collaborative Group on Hormonal Factors in Breast Cancer in Lancet 350:1047-1059, 1997; Lee et al in Int Nurs Rev 55:355-359, 2008; Hulka and Stark in Lancet 346:883-887, 1995; Kelsey in Epidemiol Rev 15:256-263, 1993; Tischer et al in J Biol Chem 266:11947-11954, 1991; Newman et al in: Proc Natl Acad Sci USA 85:3044-3048, 1988). Therefore, the aim of this study was to investigate mutations of BRCA1/2 in high risk Iranian families. We screened 85 patients who met our minimal criteria. The entire coding sequences and each intron/exon boundaries of BRCA1/2 genes were screened by direct sequencing. In the present study, we could detect the novel following mutations: p.Glu1735 p.Gly1140Ser, p.Ile26Val, p.Leu1418X, p.Glu23Gln, p.Leu3X, p.Asn1403His, p.Lys581X, p.Pro938Arg, p.Thr77Arg, p.Arg7Cys, p.Ser177Thr, IVS7+83(TT), IVS8-70(-CATT), IVS2+9(-GC), IVS1-20(-GA), IVS1-8(-AG), IVS2+24(AG), IVS5-8 (A-G), IVS2(35-39)TTcctatGAT in BRCA1 and p.Glu1391Gly, 1994_1995 (Ins A), IVS6-70-T>G in BRCA2. In agreement with findings in other populations, we found that family history is a good predictor of being a mutation carrier. Five pathogenic BRCA1 mutations and one pathogenic BRCA2 mutation were detected in 85 index cases.
  Familial Cancer 09/2011; 11(1):57-67. · 1.30 Impact Factor
• Article: The prevalence of common CFTR mutations in Iranian infertile men with non-CAVD obstructive azoospermia by using ARMS PCR techniques.

  Kyumars Safinejad, Mojtaba Darbouy, Sayed Mahdi Kalantar, Sirus Zeinali, Reza Mirfakhraie, Leila Yadegar, Masoud Houshmand
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  ABSTRACT: 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.
  Journal of Assisted Reproduction and Genetics 10/2011; · 1.84 Impact Factor
• Article: Variable expressivity and high penetrance of CYP1B1 mutations associated with primary congenital glaucoma.

  Fatemeh Suri, Shahin Yazdani, Mehrnaz Narooie-Nejhad, Seyed Jalal Zargar, Seyed Hassan Paylakhi, Sirous Zeinali, Mohammad Pakravan, Elahe Elahi
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  ABSTRACT: To investigate penetrance and expressivity of CYP1B1 genotypes associated with primary congenital glaucoma (PCG). Observational case series, systematic review, and comparative analysis of the literature. Forty probands affected with PCG, 16 siblings affected with PCG, and 103 siblings and 75 parents of the probands reported not to be affected by history. The participants were members of 40 unrelated families. Mutations were screened by restriction fragment length polymorphism, allele-specific polymerase chain reaction amplification, and direct sequencing. Ophthalmologic examination included slit-lamp biomicroscopy, intraocular pressure (IOP) measurement, gonioscopy, and high magnification stereoscopic fundus examination, followed by standard achromatic perimetry. Identification of subjects carrying CYP1B1 mutations. Glaucoma diagnosis based on slit-lamp examination, IOP measurement, gonioscopic findings, optic nerve appearance, and perimetry. Fifteen different homozygous or compound heterozygous mutant CYP1B1 genotypes were identified. Most probands and previously diagnosed subjects harbored G61E, R368H, R390H, and R469W mutations. Among the 178 apparently unaffected family members, 20 subjects from 12 families were observed to harbor 2 CYP1B1 mutations, suggesting an average penetrance of 73% for all the mutations. These 20 subjects ranged in age from 14 to 54 years. R390H appeared to have a notably high penetrance. Penetrance was 50% in the subset of families with incomplete penetrance. Ophthalmologic examination on 14 of the 20 apparently nonpenetrant individuals showed that 8 subjects were affected with juvenile open-angle glaucoma (JOAG) or primary open-angle glaucoma (POAG), and that 3 subjects were glaucoma suspect. One of the individuals with a JOAG diagnosis was the identical twin sibling of a proband affected with PCG. At least 57% of the PCG nonpenetrant individuals examined clinically were affected with JOAG or POAG to varying degrees, and overall penetrance of "affected CYP1B1 genotypes" with respect to glaucoma may be more than 90%. These findings suggest that "affected CYP1B1 genotypes" exhibit variable expressivity rather than nonpenetrance. The clinical implication of this observation is that seemingly unaffected relatives of patients with PCG, particularly those known to harbor CYP1B1 mutations, should undergo regular ophthalmologic examination to allow early diagnosis.
  Ophthalmology 10/2009; 116(11):2101-9. · 5.45 Impact Factor
• Article: Comparison of MLPA Method for Detection of Known and Unknown Deletions in Beta Globin Gene Cluster with Old Methods (REAL-TIME, RFLP, Gap-PCR)

  Alimohammadi R, Raiesi M, Ebrahimi A, Fallah S, Kianfar S, Masoudifar M, Jamali S, Babashah S, Karimipour M, Mahdian R, Zeinali S
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  ABSTRACT: Background and ObjectivesThalassaemia is one of the most common single gene disorders, which is most prevalent in the Mediterranean, the Middle East, Indian subcontinent (malaria belt). One of the mutations that result in Thalassaemia is the deletion in beta globin gene cluster. These deletions cause abnormal expressions of β, δ, ε, γ genes. At least 60 different deletions involving the beta globin gene cluster have been described to date. The molecular tests commonly used to identify these deletions are based on direct and indirect methods. With difficulties in detecting deletions and inadequate information about deletions in Iran, finding a method that can detect deletions very easily is very important.MethodsThe patients’ samples for which no abnormalities had been found using conventional DNA techniques were analyzed with MLPA assay. MLPA was done by ABI thermocycler and the result of MLPA were analyzed by Gene Marker software. Confirmation of MLPA results were done by Real-Time PCR.ResultsIn 17 patients’ samples, we found deletions leaving the beta globin gene cluster completely or partially. Most of the deletions were Sicilian, Lepore and 1 Asian-Indian and Turkish, and some were new ones.CoclusionMLPA is a rapid and sensitive method for high resolution analysis of the beta globin gene cluster. Keywords: Bata-Globins; Beta-Globins-Genetics; Thalassemia-Genetics.
  Qom University of Medical Sciences Journal. 01/2009;
• Source

  Available from: Ali Asghar Kiani

  Article: The molecular analysis of beta-thalassemia mutations in Lorestan Province, Iran.

  Ali Asghar Kiani, Yousef Mortazavi, Sirous Zeinali, Yaghob Shirkhani
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  ABSTRACT: Beta-Thalassemia (thal) is one of the most common genetic disorders in Iran and other countries. Getting information on the distribution of mutations in different ethnic groups of Iran is of fundamental importance for the purpose of health planning and prenatal diagnosis programs. One hundred and thirty chromosomes from 65 unrelated homozygous beta-thal patients were investigated for beta-globin gene mutations by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). The most common mutations of the Mediterranean region were examined in this study. Our results showed that the frameshift codons (FSC) 36/37 (-T) mutation, with a frequency of 33.8%, is the most common mutation in Lorestan Province. The other most frequent mutations were of the Mediterranean type and consisted of IVS-II-1 (G -->A), IVS-I-110 (G -->A), FSC 8/9 (+G) and IVS-I-5 (G -->C) with frequencies of 27.7, 11.5, 10.8 and 4.5%, respectively. The less frequent alleles, IVS-II-745 (C -->G), FSC 5 (-CT), IVS-I (25 bp deletion) and FSC 44 (-C) accounted for only 3.9% of the mutations. The unknown alleles comprised 7.7% of the mutations. These data showed that the spectrum of mutations found in Lorestan Province was different from those reported from other thalassemic regions of Iran and also of some neighboring countries.
  Hemoglobin 01/2007; 31(3):343-9. · 1.30 Impact Factor