Analysis of CABP2 c.637+1G>T mutation in iranian patients with non-syndromic sporadic hearing loss

The most common sensorineural defect in human is congenital hearing loss and genes have an incontestable role in the development of this defect. Many genetic mutations are known to be responsible in this heterogeneous disease. The most frequent mutations are GJB2 mutations followed by the SLC26A4 mutations. Recently, we published a report regarding the role of c.637+1G>T mutation in CABP2 gene, causing hearing loss in three Iranian families. The present study was launched to analyze the role of this recently reported mutation in patients with sporadic hearing loss. One hundred and eighty three patients with moderate to profound sporadic hearing loss were included in this study. The mutation c.637+1 G>T was investigated in patients using the PCR-RFLP method. PCR-RFLP findings revealed that the considered mutation was absent in subjects with sporadic hereditary hearing loss. The mutation c.637+1 G>T in CABP2 gene did not play any roles in the investigated Iranian patients with sporadic hearing loss. Larger samples of different populations, and assessment of all exons and the promoter region of mentioned gene will help to determine the real role of this gene in producing hearing loss. © 2014, Iranian Neurogenetics Society. All rights reserved

Novel Single Base Pair Deletion in ATM Cause Ataxia Telangiectasia in an Iranian Proband

Ataxia-telangiectasia is a rare disorder with neurological manifestations and caused by mutations in ATM gene. This gene produce a serine/threonine protein kinase, an activator of the DNA damage response in the face of DNA DSBs, which phosphorylates downstream substrates integrating with DNA repair procedure. Most ATM mutations are private mutations and, there is no mutational hotspots in the ATM gene. We unveiled a new mutation in this gene in an 8 years old A-T patient. This mutation led to fundamental alterations in ATM protein structure and representation of AT lastly.

Genetic linkage analysis of DFNB93 locus in a group of families with autosomal recessive non-syndromic hearing loss in Chahar Mahal & Bakhtiari and Kohkiluyeh & Boyer Ahmad provinces of Iran

زمینه و هدف: ناشنوایی یک اختلال حسی، عصبی است و بیشترین اختلال موجود در هنگام تولد است. بیش از 60 موارد ناشنوایی ارثی است. انواع ژنتیکی آن به دو نوع سندرومی و غیر سندرومی تقسیم می شود که نا شنوایی غیر سندرومی مغلوب اتوزومی (ARNSHL) با بیشترین درصد (70) رخ می دهد. این مطالعه با هدف تعیین پیوستگی ژنتیکی به لوکوس DFNB93 در خانواده های مبتلا به ARNSHL انجام شد. روش بررسی: این مطالعه توصیفی آزمایشگاهی بر روی 40 شجره بزرگ مبتلا به ARNSHL دارای حداقل دو بیمار، والدین سالم و عمدتاً دارای ازدواج خویشاوندی و منفی از نظر جهش های ژن GJB2، از استان های چهارمحال و بختیاری و کهگیلویه و بویراحمد انجام گردید. سپس خانواده ها برای پیوستگی ژنتیکی به لوکوس DFNB93 با استفاده از نشانگرهای STR و روش PCR و سپس ژل پلی اکریل آمید بررسی شدند. یافته ها: از تعداد 40 خانواده، 1 خانواده (5/2) به لوکوس DFNB93 پیوستگی نشان داد. ارزش SLINK این خانواده 67/2 و LOD بیشینه دو نقطه ای 05/2 و LOD بیشینه چند نقطه ای 05/2 محاسبه شد. نتیجه گیری: بر اساس نتیجه پژوهش حاضر، این لوکوس احتمالاً نقش کمی در ایجاد ناشنوایی در جمعیت مورد مطالعه (دو استان) دارد ولی برای تعیین نقش دقیق تر این لوکوس در ایجاد ناشنوایی در جمعیت ایرانی، مطالعات بیشتری ضروری می باشد

Application of Epstein-Barr Virus for Optimization of Immortalized B-lymphocyte Production as a Positive Control in Genetic Studies.

BACKGROUND Infection of B-cells with Epstein-Barr virus (EBV) leads to more and subsequent immortalization. This is considered as the method of choice for generating lymphoblastoid cell lines (LCLs). Producing LCLs, although very useful but is very time consuming and troublesome, drives the requirement for quicker and more reliable methods for EBV-driven B-cell transformation. MATERIALS AND METHODS After successfully production of LCLs, different parameters including temperature, serum concentration, type of culture medium, and CO2 concentration were evaluated on EBV-transformed B-cells. In this study, we were able to produce LCLs and optimize condition. RESULTS The best condition for generating LCLs was 37°C, 5% CO2, 20% fasting blood sugar, and RPMI 1640. The study results were to establish a reliable method for producing LCLs that can be used to produce immortalized B-cells from almost any sources. CONCLUSION This can help with tumorgenecity studies, as well as producing control material for rare genetic disorders and so on. The aim of this study was to determine optimized condition for reliable and reproducible LCLs from different sources

Kleefstra Syndrome: The First Case Report From Iran

Kleefstra Syndrome is characterized by severe mental retardation, brachycephaly, microcephaly, epileptic seizures, distinct facial features, and infantile weak muscle tone and heart defects. Deletion of EHMT1 is the main player in 75% of cases. Because of blurriness in genotype-phenotype correlation through clinical and molecular features of both 9q34.3 microdeletion patients and those with an intragenic EHMT1 mutation in Kleefstra Syndrome, genetic characterization of patients with clinical symptoms of such spectrum is desirable. We report the first Kleefstra Syndrome patient in Iran characterized through genetic approaches. Our report could improve KS diagnosis in Iran and prepare PND and PGs options for involved families

Another Novel Missense Mutation in ARSB Gene in Iran

Mucopolysaccharidosis VI (MPS-VI) is an infrequent autosomal recessive disorder caused by mutations in ARSB gene and deficiency in lysosomal enzyyme ARSB activities subsequently. This enzyme is essential for the breaking of glycosaminoglycans (GAGs) such as dermatan sulfate and chondroitin sulfate. ARSB dysfunction results in imperfect breakdown of GAGs and their accumulation in urine. Mutations in ARSB gene are the main players in MPS-VI disease and its clinical consequences. Most reported mutations are point mutations but there are some other examples in literature. Here we report a novel missense mutation in ARSB gene that is inherited as an autosomal recessive mode and probably explain the clinical status of the proband. This mutation replaces the threonine 92 by proline and alters ARSB structure. This is the most feasible scenario for clinical condition we described here. This novel mutation should be remarked for PND and PGD to improve the health and management of such families