A novel 355-357delGAG mutation and frequency of connexin-26 (GJB2) mutations in Iranian patients

The common form of autosomal recessive non-syndromic deafness is caused by the mutation in gap junction beta 2 (GJB2) gene (GenBank M86849, OMIM# 121011) which is located at the DFNB1 locus at 13q11. GJB2 is a small gene about 5500-bp length with two exons, of which only one contains the coding region (Kelley et al. 2000). The sequence of the coding region consists of 681 bp, encoding a gap-junction protein with 226 amino acids (Schrijver 2004). The genetics of hearing loss is highly heterogeneous and more than 100 mutations in connexin 26 (GJB2) genes are reported to be responsible for 30%–40% of hereditary hearing loss in deaf subjects (Ballana et al. 2001; Schrijver 2004). The most frequent mutation 35delG has been detected in different populations; especially in European countries where it is established to be due to founder effect (Van Laer et al. 2001; Rothrock et al. 2003). In this study, we performed mutation screening in 33 families who met clinical criteria of non-syndromic hereditary hearing loss (NSHHL) to evaluate the type and frequency of GJB2 mutations in Iranian population

Contra-lateral Auditory Brainstem Responses in Dyslexia

How to Cite This Article: Akbari M, Joghataei MT, Poorbakhat A, Jenabi MS. Contra-lateral auditory Brainstem Responses in Dyslexia. Iran J Child Neurol. Autumn 2016; 10(4): 10-15. AbstractObjectiveDyslexia is a neurological dysfunction (also known as a learning disability) that characterized by disability in reading in spite of normal intelligence. Bothe genetic and environmental risk factors are contributing into the condition.Diagnosis of dyslexia is based on examination and investigation of the patient’s memorial, spelling, visual, and reading skills. It is the most common learning disability, affecting 3%–10% of the school population. Modern neuroimaging techniques such as functional magnetic resonance imaging (fMRI) have shown a correlation between both functional and structural differences in the brains of children with reading difficulties. Hence, to address this issue, the auditory brainstem responses of children with dyslexia were investigated.  Materials &Methods Fifty two children with dyslexia (30 males, 22 females) were selected after examination by speech therapist. In addition, fifty two control children were included as well. The IPSI and contralateral ABR tests were conducted on both cases and controls. Click stimuli were used at 75 nHL intensity. The study focused on absolute latency of wave V in both groups. ResultsAbsolute latency of wave V in contralateral showed differences between children with dyslexia and control group, but no significant results were found in IPSI testing. ConclusionThe current data provide an evidence for brainstem and its function in signal processing and the role of brainstem nucleus on processing and delivering the information to each hemisphere.  References1. Lyon GR, Shaywitz SE, Shaywitz BA. 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Frequency of the common mitochondrial DNA (mtDNA) mutations in non-syndromic hearing impairment in southwest subpopulations of Iran

زمینه و هدف: اگرچه اکثر ناشنوایی های غیر سندرومی ارثی به علت جهش در ژن های هسته ای می باشند، در سال های اخیر مشارکت مهم جهش های DNA میتوکندریایی (mtDNA) واضح تر شده است. مطالعه حاضر با هدف غربالگری جهش های شایع mtDNA شامل A1555G، C1494T، A3243G و A7445G در ناشنوایان اکتسابی و غیرسندرومی مغلوب اتوزومی پیش از زبان باز کردن در استان چهارمحال و بختیاری و ناشنوایان غیرسندرومی پس از زبان باز کردن در استان بوشهر انجام شده است. روش بررسی: در این مطالعه توصیفی-آزمایشگاهی 150 ناشنوای اکتسابی و مغلوب اتوزومی پیش از زبان باز کردن از استان چهارمحال و بختیاری و 46 پروباند غیر خویشاوند با ناشنوایی غیرسندرومی پس از زبان باز کردن از استان بوشهر (با نتیجه منفی برای جهش های GJB2) به روش آسان انتخاب شدند. نمونه ها با روش PCR –RFLP برای جهش های شایع mtDNA غربالگری شدند. جهش های مشاهده شده، برای تایید تعیین توالی گردیدند. یافته ها: هیچکدام از جهش ها در ناشنوایان اکتسابی و غیرسندرومی مغلوب اتوزومی پیش از زبان باز کردن در استان چهارمحال و بختیاری یافت نشدند، لیکن جهشA1555G با فراوانی 35/4 در ناشنوایان غیر سندرومی پس از زبان باز کردن در استان بوشهر مشاهده شد. نتیجه گیری: این بررسی نشان می دهد که جهش های میتوکندریایی نقش برجسته تری در منشاء ناشنوایی غیر سندرومی پس از زبان باز کردن در مقایسه با پیش از زبان باز کردن در جمعیت مورد مطالعه را ایفاء می کنند

Correlation of del13q, del11q and Trisomy 12 with Laboratory and Clinical Features of Chronic Lymphocytic Leukemia in Iranian Patients

Background: There is a strong association between chromosomal abnormalities and laboratory features and clinical course of the B-cell chronic lymphocytic leukemia (B-CLL). The aim of this study was to investigate the frequency and correlation of cytogenetic aberrations with laboratory and clinical features of the disease. Methods: Clinical and laboratory features of 65 CLL patients were collected from their hospital profiles and their blood and/or bone marrow were examined by conventional cytogenetics and interphase FISH methods. Results: Conventional cytogenetic methods identified 27.7% chromosomal abnormalities in 65 patients. I-FISH analysis for del13q, del11q and trisomy 12 revealed abnormality in 75.4% of patients. The results showed that IFISH improved the detection rate of chromosomal abnormalities and it enhanced detection. Statistical analysis was performed on sex, age, family history, Rai stage and CD markers on trisomy 12, del 11q and del 13q subgroups. There was a high frequency of Ray stages I and II within del13q subgroup, Rai stages III and IV within del11q subgroup and Rai stage II within trisomy 12 subgroup. Mean of CD38 in patients with del 11q was significantly higher than mean of patients with trisomy 12 and del 13q. Conclusion: High level of CD38 and presence of del11q indicated a poor prognosis and low level of CD38 and presence of del13q was indicative of good prognosis in Iranian B-CLL patients. Trisomy 12 had an intermediate prognostic value

Analysis of CD38 and ZAP70 mRNA expression among cytogenetic subgroups of Iranian chronic-lymphocytic-leukemia patients

Chromosomal abnormalities and ZAP70 expression profile are two major independent prognostic markers in B-cell chronic lymphocytic leukemia. We investigated a possible correlation between these two markers. ZAP70 expression using real-time RT-PCR was examined in 20 B-cell chronic lymphocytic leukemia patients with del13q14, 13 patients with del11q22, 15 patients with trisomy 12, and 16 patients with no detected chromosomal abnormalities. Molecular analysis revealed that ZAP70 expression in the del13q subgroup was the same as in the control group, while it increased 2.78-fold in the del11q subgroup and 2.95-fold in the trisomy 12 subgroup, compared to the 15 cases in the control group. Comparison of the mean and standard deviation of the ZAP70 expression profile within the subgroups showed it to be highly variable among the individuals of the del11q and trisomy 12 subgroups, versus tight clustering for the del13q subgroup. Therefore, there is a correlation between del13q aberration, which has good prognosis with normal levels of ZAP70 expression. Due to a high degree of variation, no conformity is seen for del11q and trisomy 12 subgroups, making this grouping poor for prognostic discrimination. As a result, neither of these markers can serve as sole discriminators to determine the course of the disease; the use of both markers improves prognostic assessment

Report of a novel mutation in Rb1 gene from an Iranian retinoblastoma patient and its effect on splicing pattern of mRNA

زمینه و هدف: رتینوبلاستوما شایع ترین تومور جامد درون چشمی در کودکان زیر شش سال است. جهش در هر دو نسخه ژن Retinoblastoma1 (RB1) مسئول شکل گیری این بیماری می باشد. طیف وسیعی از جهش ها تاکنون در سرتاسر ژن RB1 گزارش شده است. بسیاری از جهش های نقطه ای گزارش شده در ژن های انسان، علی رغم نوع آنها، وضعیت پیرایش را دستخوش تغییر می کنند. در این مطالعه جهش جدید در ژن RB1 در یک بیمار مبتلا به رتینوبلاستوما معرفی و تاثیر آن روی پیرایش mRNA بیان می شود. گزارش مورد: در مطالعه حاضر، آنالیز جهش ژن RB1 بر روی یک بیمار ایرانی مبتلا به فرم تک گیر و یک طرفه رتینوبلاستوما (دختر بچه 4 ساله) با استفاده از تعیین توالی نواحی کد کننده و همچنین Multiplex Ligation dependent of Probe Amplification (MLPA) انجام گرفته است. در ادامه با استفاده از روش RT-PCR وضعیت پیرایش mRNA ژن RB1 نیز مورد بررسی قرار گرفت. در نتیجه این بررسی ها یک جهش هم معنی (g.70320C>T) در نزدیکی انتهای اگزون 12 شناسایی شد. این تغییر نوکلئوتیدی، توالی مورد توافق یک عنصر افزاینده پیرایش، که محل اتصال پروتئین SC-35 می باشد را از بین می برد. بررسی ساختاری cDNA این بیمار نشان دهنده اختلال در فرایند پیرایش و حذف اگزون 12 از رونوشت بالغ ژن RB1 است. نتیجه گیری: بر اساس یافته های این مطالعه می توان تغییر هم معنی فوق را تحت عنوان یک جهش پاتوژن جدید در نظر گرفت، همچنین برای اولین بار وجود یک توالی مورد توافق افزاینده پیرایش، در اگزون 12 ژن RB1 گزارش می شود

First report of preimplantation genetic diagnosis of mucopolysaccharidoses IVA and HLA typing for hematopoietic stem cell transplantation

Background: Mucopolysaccharidoses IVA is an autosomal recessive lysosomal storage disease resulting in skeletal and cartilage dysplasia. Hematopoietic stem cell transplantation is a good therapeutic option for MPS IV. Here we report the first application of PGD test for MPS IVA and HLA with the purpose of HSCT for the affected son in a family with consanguineous marriage. Haplotype analysis of linked STR markers in GALNS gene and HLA loci as well as variant detection by cycle sequencing were included in our PGD test. Results: Two out of nine embryos were transferrable. The second embryo transfer was successful and resulted in the pregnancy of one healthy and HLA matched girl. Conclusions: Preimplantation genetic diagnosis could be considered as a noninvasive clinical option for families with a mucopolysaccharidoses IVA patient to have a healthy child that is HLA-matched with the patient in need of hematopoietic stem cell transplantation. In lack of an appropriate hematopoietic stem cell donor the importance of preimplantation genetic diagnosis is much more significant too

A Monte Carlo study on dose enhancement and photon contamination production by various nanoparticles in electron mode of a medical linac

The aim of this study is the evaluation of electron dose enhancement and photon contamination production by various nanoparticles in the electron mode of a medical linac. MCNPX Monte Carlo code was used for simulation of Siemens Primus linac as well as a phantom and a tumor loaded with nanoparticles. Electron dose enhancement by Au, Ag, I and Fe2O3 nanoparticles of 7, 18 and 30 mg/ml concentrations for 8, 12 and 14 MeV electrons was calculated. The increase in photon contamination due to the presence of the nanoparticles was evaluated as well. The above effects were evaluated for 500 keV and 10 keV energy cut-offs defined for electrons and photons. For 500 keV energy cut-off, there was no significant electron dose enhancement. However, for 10 keV energy cut-off, a maximum electron dose enhancement factor of 1.08 was observed for 30 mg/ml of gold nanoparticles with 8 MeV electrons. An increase in photon contamination due to nanoparticles was also observed which existed mainly inside the tumor. A maximum photon dose increase factor of 1.07 was observed inside the tumor with Au nanoparticles. Nanoparticles can be used for the enhancement of electron dose in the electron mode of a linac. Lower energy electron beams, and nanoparticles with higher atomic number, can be of greater benefi t in this field. Photons originating from nanoparticles will increase the photon dose inside the tumor, and will be an additional advantage of the use of nanoparticles in radiotherapy with electron beams

A Monte Carlo study on dose enhancement and photon contamination production by various nanoparticles in electron mode of a medical linac

The aim of this study is the evaluation of electron dose enhancement and photon contamination production by various nanoparticles in the electron mode of a medical linac. MCNPX Monte Carlo code was used for simulation of Siemens Primus linac as well as a phantom and a tumor loaded with nanoparticles. Electron dose enhancement by Au, Ag, I and Fe2O3 nanoparticles of 7, 18 and 30 mg/ml concentrations for 8, 12 and 14 MeV electrons was calculated. The increase in photon contamination due to the presence of the nanoparticles was evaluated as well. The above effects were evaluated for 500 keV and 10 keV energy cut-offs defined for electrons and photons. For 500 keV energy cut-off, there was no significant electron dose enhancement. However, for 10 keV energy cut-off, a maximum electron dose enhancement factor of 1.08 was observed for 30 mg/ml of gold nanoparticles with 8 MeV electrons. An increase in photon contamination due to nanoparticles was also observed which existed mainly inside the tumor. A maximum photon dose increase factor of 1.07 was observed inside the tumor with Au nanoparticles. Nanoparticles can be used for the enhancement of electron dose in the electron mode of a linac. Lower energy electron beams, and nanoparticles with higher atomic number, can be of greater benefit in this field. Photons originating from nanoparticles will increase the photon dose inside the tumor, and will be an additional advantage of the use of nanoparticles in radiotherapy with electron beams

A concentration of serum selenium in multiple sclerosis patients compare to healthy subject in Tehran

     Multiple sclerosis (MS) is an inflammatory demyelinating disease which the exact etiology is still are far to be clear. Reasons for this autoimmune disease are unknown origin. The aim of present study was to evaluate serum levels of selenium in patient with MS compare to healthy subjects. A total of 46 subjects were enrolled in the study, Sera of 23 MS cases and 23 healthy normal cohorts as control group were obtained. Atomic absorption spectrophotometer was employed for estimating serum selenium level. Serum selenium levels were significantly lower in MS than in control cohorts (60.87±13 compared with 85.74±12, P-value < 0.0001). Serum selenium levels may thus be a marker of MS; the decreasing levels of serum selenium may be host defense strategies of body