Novel Mutation in FRDA Gene among Iranian Patients with Friedreich's Ataxia

Introduction: Friedrich Ataxia’s diagnosis is typically based on clinical symptoms and extended GAA repeats. However, in some rare cases the disease is caused as a result of the mutation in the exons of the FRDA (Friedreich's ataxia) gene. The current study aimed to examine point mutations in exon 1 of the FRDA gene with the goal of finding a better way for diagnosing people suspected of this disease. Materials and Methods: In this study, 30 suspected patients of Friedrich Ataxia underwent PCR molecular test. Subsequently, sequencing and long PCR were utilized to assess exon 1 in five patients with extended repeats. Results: In total, 25 participants who had extended repeats were diagnosed with Friedrich Ataxia. In one out of the five patients, the nucleotide change from G to T was observed in the nucleotide number 815324. Conclusion: Since the change had a heterozygous nature, it did not cause any deficiency in Frataxin protein. Given that family marriages are prevalent in Iran, there is a possibility of homozygosity with this mutation or other mutations. It is thus recommended that gene sequencing should be performed for individuals with suspected Friedrich Ataxia

Clinical feature and Genetics in Rett syndrome; A report on Iranian patients

Background: Rett Syndrome is characterized by normal development for the first 6–18 months of life followed by the loss of fine and gross motor skills and the ability to engage in social interaction. Mutations methyl CpG-binding protein 2 gene (MECP2) have been found in the majority of patients. This study was performed to investigate the relation of Rett clinical diagnosis and its relation with mutations in MECP2. Materials and Methods: children suspected to Rett syndrome were invited to take part in this study. Those who had met classic Rett syndrome diagnostic criteria were enrolled. Severity of symptoms was assessed for all patients. Of peripheral blood samples collected in EDTA tubes, the genomic DNA was extracted by standard salting out method. MEPC2 gene mutation was studied by DNA sequencing method. Results and conclusion: 23 patients accepted to participate in the study. 11(47.8%) patients had MECP2 gene mutation meanwhile 12 ones (52.2%) had no mutation. change in genetics was in association with phenotypical manifestations. The most prevalent mutation was p.v288 which is mostly in association with partially or uncontrolled seizures. This was the first time that Rett syndrome patients were studied in both clinical manifestations and genetic changes in Iran

No mitochondrial DNA deletions but more D-loop point mutations in repeated pregnancy loss

Abstract Purpose Repeated pregnancy loss (RPL) occurs in 1 out of 300 couples, and the cause of about 50% of them remains idiopathic. Mitochondria have an important role in human development through ATP production and their involvement in apoptosis. Methods 96 RPL and 96 control females were used to investigate the frequency of deletions and point mutations in the displacement loop (D-loop) on mitochondria. Multiplex PCR and DNA sequencing methods were used to detect possible variations in the mitochondrial DNA (mtDNA). Results No deletions but a high frequency of point mutations were found in RPL females; among 129 variations observed in RPL, 22 mutations were significant (P<0.05) and the insertion of C in nucleotide 114 was novel. Conclusion High rate of mutations in D-loop of mtDNA was observed in maternal blood, a fact that may have a direct or indirect role in inducing RPL. The results can be used in the assessment of RPL and designing possible treatments for improving assisted reproduction

Lysosomal Storage Disease in Iran (Report of Molecular Study)

How to Cite this Article: Houshmand M, Tonekaboni SH, Karimzadeh P, Aryani O, AshrafiMR, Salehpour Sh, Badv Sh, Shakiba M, Alaee MR, Farshid Sh. Lysosomal Storage Disease inIran. (Report of Molecular Study). Iran J Child Neurol Autumn 2012; 6:4 (suppl. 1): 22. Pls see PDF

Sodium Channel Gene Mutations in Children with GEFS+ and Dravet Syndrome: A Cross Sectional Study

 How to Cite This Article: Tonekaboni SH, Ebrahimi A, Bakhshandeh Bali MK, Houshmand M, Moghaddasi M, Taghdiri MM, Nasehi MM. Sodium Channel Gene Mutations in Children with GEFS+ and Dravet Syndrome: A Cross Sectional Study. Iran J Child Neurol. 2013 Winter; 7 (1):25-29. Objective Dravet syndrome or severe myoclonic epilepsy of infancy (SMEI) is a baleful epileptic encephalopathy that begins in the first year of life. This syndrome specified by febrile seizures followed by intractable epilepsy, disturbed psychomotor development, and ataxia. Clinical similarities between Dravet syndrome and generalized epilepsy with febrile seizure plus (GEFS+) includes occurrence of febrile seizures and joint molecular genetic etiology. Shared features of these two diseases support the idea that these two disorders represent a severity spectrum of the same illness. Nowadays, more than 60 heterozygous pattern SCN1A mutations, which many are de novo mutations, have been detected in Dravet syndrome. Materials & Methods From May 2008 to August 2012, 35 patients who referred to Pediatric Neurology Clinic of Mofid Children Hospital in Tehran were enrolled in this study. Entrance criterion of this study was having equal or more than four criteria for Dravet syndrome. We compared clinical features and genetic findings of the patients diagnosed as Dravet syndrome or GEFS+. Results 35 patients (15 girls and 20 boys) underwent genetic testing. Mean age of them was 7.7 years (a range of 13 months to 15 years). Three criteria that were best evident in SCN1A mutation positive patients are as follows: Normal development before the onset of seizures, onset of seizure before age of one year, and psychomotor retardation after onset of seizures. Our genetic testing showed that 1 of 3 (33.3%) patients with clinical Dravet syndrome and 3 of 20 (15%) patients that diagnosed as GEFS+, had SCN1A mutation. Conclusion In this study, normal development before seizure onset, seizures beginning before age of one year and psychomotor retardation after age of two years are the most significant criteria in SCN1A mutation positive patients.References Dravet C, Bureau M, Oguni H, Fukuyama Y, Cokar O.Severe myoclonic epilepsy in infancy (Dravet syndrome). In: Roger J, Bureau M, Dravet C, Genton P, Tassinari CA, Wolf P, eds. Epileptic Syndromes in Infancy, Childhood and Adolescence, 4th  ed. London: John Libbey Eurotext Publishers; 2005. p. 89-113.Dalla Bernardina B, Colamaria V, Capovilla G, Bondavalli S. Nosological classification of epilepsies in the first three years years of life. Prog Clin Biol Res 1983;124:165-83.Commission on Classification and Terminology of the International League against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1989;30:389-99.Scheffer IE, Zhang. YH, Jansen FE, Dibbens L. Dravet syndrome or genetic (generalized) epilepsy with febrile seizures plus? Brain Dev 2009;31(5):394-400.Singh R, Andermann E, Whitehouse WP, Harvey AS, Keene DL, Seni MH, et al. severe myoclonic epilepsy of infancy: extended spectrum of GEFS+? Epilepsia 2001;42(7):837-44.Scheffer IE, Harkin LA, Dibbens LM, Mulley JC, Berkovic SF. Neonatal epilepsy syndromes and generalized epilepsy with febrile seizures plus (GEFS+). Epilepsia 2005;46 Suppl 10:41-7.Harkin LA, McMahon JM, Iona X, Dibbens L, Pelekanos JT, Zuberi SM, et al. The spectrum of SCN1A-related infantile enceptic encephalopathies. Brain 2007;130(Pt 3):843-52.Sun H, Zhang Y, Liang J, Liu X, Ma X, Qin, et al. Seven novel SCN1A mutations in Chinese patients with severe myoclonic epilepsy of infancy. Epilepsia 2008;49:1104-7.Miller SA, Dykes DD, polesky HF. A simple salting out procedure  for  extracting  DNA from  human  cucleated Nucleated cells. Nucleic Acids Res 1988;16(3):2115.Marini C, Scheffer IE, Nabbout R, Mei D, Cox K, Dibbens LM, et al. SCN1A duplications and deletions detected in dravet syndrome: implications for molecular diagnosis. Epilepsia 2009; 50(7):1670-8.Striano P, Mancardi MM, Biancheri R, Madia F, Gennaro E, Paravidino R, et al. Brain MRI findings in severe myoclonic epilepsy in infancy and genotype- correlations. Epilepsia 2007;48(6):1092-6.Wang JW, Kurahashi H, Ishii A, Kojima T, Ohfu M, Inoue T, et al. Micro chromosomal deletions involving SCN1A and adjacent genes in severe myoclonic epilepsy in infancy. Epilepsia 2008;49(9):1528-34.Lossin C. A catalog  of  SCN1A variants.  Brain  Dev 2009;31:114-30.Fountain-Capal JK, Holland KD, Gilbert DL, Hallinan BE When should clinicians order genetic testing for Dravet syndrome? Pediatr Neurol 2011;45(5): 319-23. Hattori J, Ouchida M, Ono J, Miyake S, Maniwa S, Mimaki  N,  et  al. A screening  test  for  the  prediction of Dravet syndrome before one year of age. Epilepsia 2008;49(4):626–33.Nabbout R, Gennaro E, Dalla Bernardina B, Dulac O, Madia F, Bertini E, et al. spectrum of SCN1A mutations severe myoclonic epilepsy of infancy. Neurology 2003;60(12):1961-7.Ohmori I, Ouchida M, Ohtsuka, Y oka E, Shimizu K. Significant correlation  of  The  SCN1A mutations  and severe myoclonic epilepsy in infancy. Biochem Biophys Res Commun 2002;295:17-23.Cales. L, Del-favero J, Ceulemans B, Lagae L, Van Broeckhoven C, De jonghe P. De novo mutations in the sodium- chnnel gene SCN1A cause severe myoclonic epilepsy of infancy. Am J Hum Genet 2001; 68(8):1327-32.Brunklaus A, Ellis R, Reavey E, Forbes GH, Zuberi SM.Prognostic, clinical and demographic features in SCN1A mutation-positive Dravet syndrome. 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Evaluation of AURKA rs2273535 and CDKN1B rs34330 Polymorphisms Association with the Risk of Breast Cancer

Background & Objective: Breast cancer consists of a heterogeneous group of tumours with different prognosis and is the most common cause of cancer-related mortality among women. In this study, our goal was to evaluate the association of AURKA rs2273535 and CDKN1B rs34330 polymorphisms with risk of female breast cancer in southwest part of Iran. Materials & Methods: This case-control study was done on 50 women with breast cancer and 50 healthy women without any symptoms or family history of breast cancer as the case and control group, respectively. Restriction fragment length polymorphism (RFLP- PCR) technique was designed to determine the AURKA rs2273535 and CDKN1B rs34330 gene polymorphisms. Afterwards, statistical analysis was done by means of SPSS (version 17). Results: In current research, our finding showed that rs2273535 T allele increased the susceptibility of breast cancer (OR:2.58, 95%CI:1.5-31.09, P=0.006). Moreover, T allele in dominant phase could raise the risk of the breast cancer (OR:3.01, 65%CI:1.31-6.92, P=0.009). However, the other polymorphism, CDKN1B rs34330, revealed no associations with increased risk of breast cancer. Conclusion: These findings suggest that AURKA rs2273535 may influence individual’s susceptibility to breast cancer. But we found no associations regarding CDKN1B rs34330 polymorphism and this type of cancer