Ataxia Oculomotor Apraxia Type 1 in the Siblings of a Family: A Novel Mutation

How to Cite This Article: Karimzadeh P, khayatzadeh kakhki S,Esmail Nejad Sh. S., Houshmand M,Ghofrani M. Ataxia oculomotor apraxia 1 in two siblings of a family:a novel mutation. Iran J Child Neurol.Winter 2017; 11(1):78-81.AbstractAlthough AOA1 (ataxia oculomotor apraxia1) is one of the most common causes of autosomal recessive cerebellar ataxias in Japanese population, it is reported from all over the world. The clinical manifestations are similar to ataxia telangiectasia in which non-neurological manifestations are absent and include almost 10% of autosomal recessive cerebellar ataxias. Dysarthria and gait disorder are the most two common and typical manifestations. Oculomotor apraxia is usually seen a few years after the manifestations start. APTX gene on 9p13.3 chromosome is expressed in the cells of all human body tissues and different mutations had been discovered. Here we report two siblings (a girl and a boy) of consanguineous parents visited at Mofid Pediatrics Hospital in 2015, with history of gait ataxia, titubation, tremor, and oculomotor apraxia around five yr old and after that. The brother showed symptoms of disease earlier and more severe than his sister did. After ruling out the common etiologies of progressive ataxia, we did genetic study for AOA1 that showed a homozygous frameshift mutation as c.418_418 del was found. This mutation was not reported before so this was a new mutation in APTX gene.References1. Jafar-Nejad P, Maririch SM, Zoghbi HM .The cerebellum and hereditary ataxias. In: Swaiman KF, Ashwal S, Ferriero DM, Schor NF. Swaiman’s Pediatric Neurology Principles, and Practice.15th ed. 2012.P.939-952.2. Pina-Garza JE. Ataxias. In:Pina-Garza JE. Fenichel Clinical pediatric neurology. 7th ed. 2013.P.215-231.3. Le Ber I, Moreira MC, Rivaud-Péchoux S, Chamayou C, Ochsner F, Kuntzer T, et al. Cerebellar ataxia with oculomotor apraxia type 1: clinical and genetic studies. Brain 2003; 126:2761-72.4. Coutinho P, Barbot C. Ataxia with Oculomotor Apraxia Type 1. 2002 Jun 11 [Updated 2015 Mar 19]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016. Available from: https:// www.ncbi.nlm.nih.gov/books/NBK1456/5. Shahwan A, Byrd PJ, Taylor AM, Nestor T, Ryan S, King MD. Atypical presentation of ataxia-oculomotor apraxia type 1. Dev Med Child Neurol 2006 Jun; 48(6):529-32. 6. Shimazaki H, Takiyama Y, Sakoe K, Ikeguchi K, Niijima K, et al. Early-onset ataxia with ocular motor apraxia and hypoalbuminemia: the aprataxin gene mutations. Neurology 2002; 59(4):590-5.7. Yokoseki A, Ishihara T, Koyama A, Shiga A, Yamada M, Suzuki C,and et al. Genotype-phenotype correlations in early onset ataxia with ocular motor apraxia and hypoalbuminaemia. Brain 2011; 134:1387-99.8. Moreira MC, Barbot C, Tachi N, Kozuka N, Mendonça P, Barros J, Coutinho P, Sequeiros J, Koenig M. Homozygosity mapping of Portuguese and Japanese forms of ataxia-oculomotor apraxia to 9p13, and evidence for genetic heterogeneity. Am J Hum Genet 2001; 68(2):501-8

Clinical and Molecular Study of NPC in Iran: Report of 5 Novel Mutations

How to Cite This Article: Tonekaboni SH, Aryani O, Karimzadeh P, Zaman T, Ashrafi M, Salehpour Sh, Dehghan Manshadi M, Khalili E, Houshmand M. Clinical and Molecular Study of NPC in Iran: Report of 5 Novel Mutations. Ir an J Child Neurol. 2015 Autumn;9:4(Suppl.1): 8-9.Pls see pdf

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Glutaric AciduriaType 1: Clinical and Molecular Study in Iranian Patients, 3 Novel Mutations

Objective Glutaricaciduria type 1 (GA1), is a rare, treatable neuro metabolic disease, due to glutaryl- CoA dehydrogenase (GCDH) gene mutation.In regions without neonatal blood screening (NBS), patients are diagnosed in symptomatic period. This study was carried out to assess patients with GA1 for clinical, biochemical, neuroimaging findings and GCDH gene mutations analysis. Materials & Methods In this cross-sectional study, clinical manifestation, neuroimaging and metabolic findings of eleven Iranian GA1 patients of MofidChildren’s Hospital, Tehran, Iranbetween 2001 and 2011,were evaluated.Mutational analysis of the GCDH gene was performed on genomic DNA. Genomic DNA was extracted from peripheral lymphocytes using QIAamp DNA Micro Kit (Qiagen). All 11 exons and flanking intronic regions of the GCDH gene were amplified by polymerase chain reaction (PCR). Results All patients were diagnosed before 32 months old. Clinical presentations of GA1 include acute encephalopathic crisis and/or developmental delay and macrocephaly. Seven GCDH gene mutations were detected in our patients. The most frequent GCDH mutations occurred in exon7 then exon8, 10 and11. G244 C in exon7, R294 Q in exon8 and N373 S in exon 10 were three novel mutations. There was no correlation between of genotype and phenotype in our patients. Conclusion Physician must remember GA1 in differential diagnosis of acute encephalopathic crisis, macrocephaly, developmental delay, movement disorders such as dystonia and dyskinesia. Early detection, proper treatment and selective screening of patients’ siblings can prevent neurologic disabilities

Expression and Prognostic Significance of Bcl-2 and Bax in The Progression and Clinical Outcome of Transitional Bladder Cell Carcinoma

Objective: To evaluate the mRNA expression ratio of Bcl-2/Bax both in normal and tumoral bladder tissues of patients with transitional cell carcinoma (TCC) of bladder and investigate potential correlation between this expression ratio and clinical outcome.Materials and Methods: In this experimental study, we used real time-PCR to investigate the expression of Bcl-2 and Bax both in normal and tumoral bladder tissues. The Bcl-2/Bax expression ratio was determined in tumoral bladder tissues of patients with transitional cell carcinoma of the bladder (n=40) and correlation between expression ratios and the emergence of early relapses in a follow-up of 14-30 months was examined.Results: Relapse-free time in 14/31 patients (45.16%) with Bcl-2/Bax>1 was shorter than 9 months (range of 2-9 months) with 5.7 months average median while 17/31 patients (54.84%) with Bcl-2/Bax<1 are currently relapse-free (14-30 months). Bcl-2 and Bax expression levels were not solely correlated with clinical outcome and progression of carcinogenesis.Conclusion: The mRNA expression ratio of Bcl-2/Bax in tumoral bladder tissues may serve as a significant prognostic indicator in predicting the clinical outcome in low grade non-invasive bladder cancer

MicroRNA Microarray Profiling during Megakaryocyte Differentiation of Cord Blood CD133+ Hematopoietic Stem Cells

Objective In order to clarify the role of microRNAs (miRNA) in megakaryocyte differentiation, we ran a microRNA microarray experiment to measure the expression level of 961 human miRNA in megakaryocytes differentiated from human umbilical cord blood CD133+ cells. Materials and Methods In this experimental study, human CD133+ hematopoietic stem cells were collected from three human umbilical cord blood (UCB) samples, and then differentiated to the megakaryocytic lineage and characterized by flow cytometry, CFU-assay and ploidy analysis. Subsequently, microarray analysis was undertaken followed by quantitative polymerase chain reaction (qPCR) to validate differentially expressed miRNA identified in the microarray analysis. Results A total of 10 and 14 miRNAs were upregulated (e.g. miR-1246 and miR-148-a) and down-regulated (e.g. miR- 551b and miR-10a) respectively during megakaryocyte differentiation, all of which were confirmed by qPCR. Analysis of targets of these miRNA showed that the majority of targets are transcription factors involved in megakaryopoiesis. Conclusion We conclude that miRNA play an important role in megakaryocyte differentiation and may be used as targets to change the rate of differentiation and further our understanding of the biology of megakaryocyte commitment

Biochemical Diagnosis of Common Gene Mutations in Galactosemia

Objective: Galactosemia is an inborn error of galactose metabolism that is inherited in an autosomal recessive trait. Classical galactosemia is caused by deficient activity of the galactose-1-phosphate uridyltransferase (GALT) enzyme that can result in galactosemia complications. Materials & Methods: 135 unrelated families, clinically suspected to galactosemia, were screened by qualitative measurement of galactose-1-phosphate uridyl transferase (GALT) activity in blood RBCs by using Beutler method. Results: Deficient enzyme activity (classical galactosemia) were confirmed in 16 families. All of these 16 families were submitted to the diagnosis of six common mutations in GALT gene including Q188R, K285N, S135L, L195P, X380R and Q169K by using PCR-RFLP method which resulted in detection of 68% of the mutated alleles. Eight patients were homozygote for Q188R mutation, while one patient homozygote for S135L mutation and one heterozygote for K285N mutation. Conclusion: Biochemnical diagnosis of Galactosemia in Grand infant hospital is very important and necessary

Prevalence of Strongyloides stercoralis in the immunocompetent and immunocompromised individuals in Iran: a systematic review and meta-analysis

Strongyloidiasis is a neglected tropical disease mostly distributed in tropical and subtropical regions. The current study evaluated the prevalence of Strongyloides stercoralis in immunocompetent and immunodeficient patients in Iran. The available online literature published from June 1994 to October 2020 was obtained from multiple English databases (PubMed, Science Direct, Scopus, Web of Science and Google Scholar) and four Persian databases (Magiran, Iran Medex, Iran Doc and SID). All statistical analyses were performed using R software (version 3.6) meta-package and p-values <0.05 were considered significant. From 1051 articles, 74 studies (248 656 individuals) met the inclusion criteria. The pooled prevalence of S. stercoralis was 2% (95% confidence interval [CI] 1 to 3) and 4% (95% CI 1 to 8) in immunocompetent and immunodeficient patients, respectively. In immunodeficient cases, the pooled prevalence of studies utilizing serology, culture and microscopic methods was 10% (95% CI 2 to 23), 1% (95% CI 0 to 6) and 1% (95% CI 0 to 1), respectively. In immunocompetent cases, the pooled prevalence of studies utilizing microscopic, culture and molecular methods was 2% (95% CI 1 to 3), 2% (95% CI 1 to 4) and 2% (95% CI 0 to 6), respectively. We propose an appropriate screening and control program along with comprehensive research regarding the frequency of strongyloidiasis in the country