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Background: Filament aggregating protein (Filaggrin) is a skeletal cell component that provides a protective function for the epidermis. Mutations of the filaggrin gene (FLG) cause a loss of filaggrin protein. These mutations are seen in 50% of atopic dermatitis (AD). The aim of the study was to investigate the polymorphisms and mutations of the FLG in Iranian childrenwith AD.Materials and methods: This project was a case-controlled study with 25 children diagnosed with AD as the case group and 25 healthy children as the control group. Demographic data, clinical manifestations, and filaggrin single nucleotide polymorphisms (SNPs) and mutations were recorded. Blood samples were collected for the immunoglobulin E (IgE) assay and complete blood count tests.Results: We found a significant association between the presence of polymorphism (rs66831674) and patients’ age, and polymorphism (rs41267154) and early onset of AD. We found no significant differences between the FLG polymorphisms with respect to the severity of AD, ethnicity, concurrent allergic diseases, eosinophilia, and IgE serum levels.Conclusion: Interestingly, FLG variants (rs66831674 and rs41267154) were associated with age and early onset of AD. However, additional studies are required to confirm these results on a large scale of Iranian population. Moreover, establishing a cohort prospective study is suggested to assess the progression of other atopic disorders based on FLG polymorphisms.

Mucopolysaccharidosis VI is a rare autosomal recessive disorder caused by the deficiency of enzyme Arylsulfatase B. The enzyme deficiency leads to the accumulation of dermatan sulfate in connective tissue which causes manifestations related to MPS VI. Up to now, three different disease causing variants are reported in Iranian patients. In this study, we scanned ARSB gene of 13 Iranian patients from 12 families in whom all parents were consanguineous and from the same ethnicity except one family that were not consanguineous but co-ethnic. We found six not previously reported disease causing variants. We extracted DNA from peripheral blood samples of patients that were previously confirmed as MPS VI by clinical, biochemical and enzymatic assays including berry-spot test and fluorimetry, followed by PCR and direct sequencing. Computational approaches were used to analyze novel variants in terms of their impact on the protein structure. 11 disease causing variants and 15 polymorphisms were found. Six disease causing variants were novel and five were previously reported of which three were in Iranian population. Four of patients, who were unrelated, two by two had the same disease causing variant and polymorphisms, which indicates a possible founder effect. Our study also implicates genotype–phenotype correlation. Computational structural modeling indicated these disease causing variants might affect structural stability and function of the protein. Data of this study confirms the existence of mutational heterogeneity in the ARSB between Iranian patients. Disease causing variants with high frequency can be used in the prenatal diagnosis and genetic counseling. Also, the existence of the same variants and polymorphisms in some of the unrelated patients indicates a possible founder effect.

Introduction Ataxia telangiectasia (AT) is an autosomal recessive multisystem disorder characterized by variable immunodeficiency, progressive neurodegeneration, occulocutaneous telangiectasia, and an increased susceptibility to malignancies. This study was designed to study the role of proapoptotic BAK, BAX, and NBK/BIK genes in a group of patients with AT to elucidate the possible role of these genes in progression of malignancies in this disease. Materials and Methods Fifty Iranian patients with AT were investigated in this study. The entire coding regions of the BAK gene (exons 2-6), NBK/BIK gene (exons 2-5), and BAX gene (exons 1-7) were amplified using polymerase chain reaction (PCR). The PCR products were separated by 2% agarose gel electrophoresis, and all positive samples were verified by direct sequencing of PCR products using the same primers used for PCR amplification, BigDye chemistry, and Avent 3100 Genetic Analyzer following the manufacturer's instructions (Applied Biosystems). Results Eight of fifty Iranian AT patients (16%) exhibited a C > T transition in exon 2 (c342C > T) of the BAK gene, while none of the healthy controls had such alteration (P = 0.0001). Higher frequency of another nucleotide substitution in the noncoding region of exon 7 in BAX gene (6855G > A) was also identified in 68% of the patient group versus 24% in the controls (P < 0.0001). Sequence alteration in intronic region of the NBK/BIK gene IVS4-12delTC was observed in 52% of AT patients, which was significantly higher than 20% in the control group (P = 0.0023). Another variant IVS1146C > T in the intronic region of the BAX gene was found in 78% of patients, which was significantly higher than 10% in the controls (P < 0.0001). Frequency of alteration in intronic region of exon 3 of the BAX gene (IVS3 + 14A > G) was also significantly higher in the AT patients (P < 0.0001). Discussion Several alterations in the proapoptotic genes BAK, NBK/BIK, and BAX were found in our study, which could elucidate involvement of the mitochondrial pathway mediated apoptosis in accelerating and developing of cancers and in immunopathogenesis of AT. Such altered apoptosis in AT could play some roles in developing cancers in this group of patients.

Issue Title: Special Issue: Inflammasome and Inflammation (Part 1); Editor: Dr. Sudhir Gupta, MD, Ph.D, MACP