Introduction: Ataxia-telangiectasia (A-T) a multisystem disorder primarily characterized by cerebellar degeneration, telangiectasia, immunodeficiency, cancer susceptibility and radiation sensitivity. Identification of the gene defective in this syndrome, ataxia-telangiectasia mutated gene (ATM), and further characterization of the disorder together with a greater insight into the function of the ATM protein have expanded our knowledge about the molecular pathogenesis of this disease.Area covered: In this review, we have attempted to summarize the different roles of ATM signaling that have provided new insights into the diverse clinical phenotypes exhibited by A-T patients.Expert commentary: ATM, in addition to DNA repair response, is involved in many cytoplasmic roles that explain diverse phenotypes of A-T patients. It seems accumulation of DNA damage, persistent DNA damage response signaling, and chronic oxidative stress are the main players in the pathogenesis of this disease.
Background: Hutchinson-Gilford Progeria Syndrome (HGPS) is a very rare genetic disorder with a frequency of 1 in 8 million live births. It is characterised by premature aging phenotype. The median age at death is 13.4 years. It is an autosomal dominat disease due to a de novo point mutation in the Lamin A gene exon 11 in the majority of cases. More than 100 cases have been reported world wide. Case report: We describe here an exceptionally long-lived patient with HGPS, who is alive at age 36. She was referred by a cardiologist to our endocrinology clinic to be worked up for presence of a metabolic or genetic disorder before a heart surgery. Results: Having more attention of clinicians about very rare diseases and referring the patients to geneticist are the main goals of this case report as well as describing the disease.
DNA copy number variation is an important cause of genetic disease. There are several techniques available to detect copy number changes of various sizes, each with their limitations in resolution and cost. Here we outline the development of multiplex amplifiable probe hybridization (MAPH) into a high-throughput diagnostic technique for detecting copy number variation of almost any size. Its application in testing for genetic mutations causing diseases, such as familial breast cancer, Charcot-Marie-Tooth disease Type 1A, Duchenne/Becker muscular dystrophy and familial colorectal cancer is described, as well as its use in identifying chromosomal changes in some individuals with mental retardation. The analysis of the data produced by MAPH is also considered, along with its potential for automation and development of microarray-based MAPH.
Background: Vitiligo is a long-term multifactorial polygenic disorder, characterized by the patchy loss of pigments in the skin. Several treatments including therapeutic creams and oral drugs are used to treat vitiligo with varying degrees of success. Some medical treatments can reduce the severity of the disease, but it is difficult to cure the disorder. Autologous non-cultured melanocyte transplantation is an effective method of vitiligo treatment. The utilization of appropriate cell suspension is a safe and efficient strategy to cure such hypopigmentation disorder. Objectives: The aim of this study was to follow up patients suffering from generalized and stable vitiligo who were treated with transplanted cells. Patients with patches in four different parts (forehead, eyelids, trunks, and hands) were selected because skin thickness varied among different body parts. We compared melanin repigmentation in these areas. Methods: We recruited 39 patients with generalized and stable vitiligo who had patches on their forehead, eyelids, trunks, and hands. Partial grafts were taken from the gluteal regions of all patients. Epidermal cells including non-cultured melanocyte and keratinocyte suspensions were enzymatically isolated and found to be of > 98% viability. Cells were injected intraepidemally. After a 12-month follow-up, repigmentation was observed. Results: The mean repigmentation score continued to improve up to 12 months post-transplantation. The obtained results confirmed that the cellular suspension that consisted of a mixture of epidermal cells improved to restore the normal color of the repigmentation rate. The number of received cells per cm2 positively influenced the repigmentation score. Patches located on the face, neck, and trunk areas showed significantly higher responses to treatment. The pigmentation score was classified as “poor” (1% - 25%), “moderate” (26% - 50%), and “good” (51% - 75%). This study is a research and clinical study with a brief report registered with the Ethics Committee of Avicenna Research Institute, clinical trials (letter number: 93/22/01/89), Tehran, Iran. Conclusions: The application of autologous non-cultured melanocyte-keratinocyte cell suspension could restore the patchy skin color to a near-normal level and the majority of the patients were satisfied with the results.
We describe humans with rare biallelic loss-of-function PTCRA variants impairing pre-α T cell receptor (pre-TCRα) expression. Low circulating naive αβ T cell counts at birth persisted over time, with normal memory αβ and high γδ T cell counts. Their TCRα repertoire was biased, which suggests that noncanonical thymic differentiation pathways can rescue αβ T cell development. Only a minority of these individuals were sick, with infection, lymphoproliferation, and/or autoimmunity. We also report that 1 in 4000 individuals from the Middle East and South Asia are homozygous for a common hypomorphic PTCRA variant. They had normal circulating naive αβ T cell counts but high γδ T cell counts. Although residual pre-TCRα expression drove the differentiation of more αβ T cells, autoimmune conditions were more frequent in these patients compared with the general population.
INTRODUCTION: Vitiligo is a hypopigmented disorder characterized by irregular loss of of the skin pigmentation. Current therapeutic modalities focus on increasing melanin production and modulating immune system responses. The use of some combined topical agents, in appropriate concentrations, is a possibility for the treatment of such hypopigmentation disorders. OBJECTIVE: To follow-up patients who used a combination of creams in the experimental times of 6 and 14 months and to determine the effectiveness of the formulation. METHODS: Forty-one patients with generalized stable vitiligo participated in the study. Patients applied a cream containing acetyl hexapeptide-1, mometazone furoate and dihydroxyacetone. The sites of the lesions included eyelids, forehead, face, neck, fingertips, hands, feet and legs. The variations in the treated patches were evaluated by dermatologists at each experimental visit. The percentage of repigmentation was evaluated after 6 months. RESULTS: After 6 months of treatment, 8 patients (19.51%) had an excellent response to treatment, while a good response was observed in 19 patients (46.34%), moderate response in 10 (24.39%), and unsatisfactory in 4 (9.75%). Eyelids, face and forehead presented the best rate of repigmentation, while fingertips response was generally unsatisfactory. CONCLUSIONS: The data support the efficacy of the new cream evaluated by the present study.
Mutations of the epidermal growth factor receptor (EGFR) gene, predominantly in exons 18-21, have been highlighted to function as the crucial predictors of the response rate of patients with non-small cell lung cancer (NSCLC) to EGFR tyrosine kinase inhibitors (TKIs).This study was performed at Tehran University of Medical Sciences. Data and information were retrospectively collected from the period between Dec 2010 and Apr 2014. Exons 18 to 21 of the EGFR were analyzed for any potential mutation by PCR, accompanied by DNA sequencing on 160 with pathological confirmation of NSCLC.Demographically, the male to female ratio was approximately 2:1, and a substantial difference in age between sexes was not observed (P=0.065), but a noticeable difference was found in the smoking variable, where 77.8% of males were smokers compared to 17.3% of women (odds ratio (OR) (95% CI) = 16.72 (7.15-39.11)). We found a frequency of 10.63% (17/160) for mutations found in exons 19 and 21, nonetheless, no mutations in exon 18 and exon 20 were observed. The most frequently observed mutations were c.2235_2249, del and c.2240_2257, del in exon 19 and p. L858R in exon 21. The c.2253A>G was found as a novel mutation that was the rarest mutation detected in this work. Interestingly, a remarkable negative association was revealed between smoking and mutation rates in NSCLC patients (OR (95% CI) = 0.13 (0.04-0.46).The occurrence of EGFR mutations is largely varied among the different states of Iran, probably due to variations in ethnicity, smoking rate, and sex ratio of participants.
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