Plasma microRNA levels in childhood IgA vasculitis.

INTRODUCTION: Immunoglobulin A vasculitis (IgAV) is the most common form of childhood systemic vasculitis. It is mostly self-limiting and characterized by skin, joint, gastrointestinal tract, and kidney involvement. Microribonucleic acids (miRNAs) are 18-25 base-long non-coding RNA group acting on gene expression. They have been shown to be effective on the immune system studies to date. METHOD: In our study, 24 IgAV children with skin and joint involvement and 24 healthy children were included. Five different miRNAs (miR-33, miR-34, miR-122, miR-204, and miR451) known to be expressed in plasma and related with autoimmunity pathogenesis were evaluated. miRNAs were compared between the active period of the disease, the post-treatment period, and the healthy group using the real-time PCR method. RESULTS: Expression levels of miRNA-33 and miRNA-34 increased significantly in active period of the patients compare with inactive period and control groups. The expression levels of miRNA-122 and miRNA-204 decreased significantly in active period of the patients compare with other two groups. There was no significant difference in miRNA-451 levels. CONCLUSIONS: With the experience we gained from our recent studies, we think that miRNA-204 may be a significant biomarker in autoimmune diseases. Our study is the first study between IgAV and miRNAs in children. More studies are needed to reveal this relationship. Key Points • This is the first paper to show the relationship between miRNAs and childhood IgAV. • It will provide a new perspective to evaluate the pathogenesis of the disease.

MicroRNA Expression Levels in Patients with Hashimoto Thyroiditis: A Single Centre Study.

OBJECTIVE: To determine the circulatory miRNA expression levels in patients with Hashimoto thyroiditis (HT) at the time of diagnosis and follow-up period compared with healthy controls. METHODS: We collected blood samples from 34 patients with HT (4 males and 30 females) at the time of first diagnosis (Group P) and euthyroid period (Group E). Thirty-three healthy controls (Group H) blood samples were also included in the study. Expression levels of five different circulating miRNAs (miR-22, miR-141, miR-155, miR-375, miR-451) were evaluated using real-time polymerase chain reaction. RESULTS: There was a significant difference in miR-375 levels between the groups P and H. Also, for miR-451, there was a significant difference between the P and E groups. Finally, there was a moderate positive correlation between thyroid-stimulating hormone values and miR-22 expression levels for the P group. CONCLUSION: miRNAs have important roles at all stages of the diseases. More studies must be performed in all thyroid diseases and autoimmune diseases, including HT.

Karyotype analysis in children with idiopathic intellectual disability.

Intellectual disability (ID) is a heterogeneous condition, affecting 1-3% of general population. In this study, karyotype analysis was performed in 33 children with idiopathic ID in a hospital with limited laboratory facilities to determine the value of karyotype analysis as a first step test in children with idiopathic ID. Thirty-three patients with idiopathic ID were included in the study. Giemsa-trypsin-Leishman (GTL) banding karyotype resolution at a standard resolution of 550 bands was performed to determine whether the patients had microdeletion/microduplication by using of conventional karyotype analysis. Of 33 children, seven (21.2%) showed various chromosomal changes. Polymorphisms including 46,XX,1qh+; 46,XX,1qh+,1qh+; 46,X,add(Y),q12; 46,XY,21ps+ and 46,XX,1qh+ were diagnosed in five children. Inversion [46,XY,inv9(p12q13)] and inversion and polymorphisms [46,XY,inv9(p12q13),13ps+] were diagnosed in two children, respectively. We believe that inv(9)(p12q13) is a benign variant. In conclusion, our findings showed that the karyotype analysis was not helpful to determine etiology in children with idiopathic ID, probably because of the low patient number in our study.

Interleukin-6 and interleukin-17 gene polymorphism association with celiac disease in children.

BACKGROUND/AIMS: This study aimed to investigate polymorphisms in the genes responsible for encoding cytokines interleukin-6 (IL-6) (-572G/C) (rs1800796) and IL-17 (-197A/G) (rs2275913) in patients with celiac disease (CD). We further aimed to investigate the relationship between CD symptoms and histopathological findings and the relationship between these polymorphisms. MATERIALS AND METHODS: We compared the results with those of healthy control subjects to establish whether any of the polymorphisms are involved in the susceptibility to CD. Eighty-four patients with CD and 83 healthy controls were enrolled in this study. Children with CD were divided into two groups depending on whether their symptoms were typical or atypical. The IL-6 (-572G/C) and IL-17 (-197A/G) polymorphisms were genotyped based on a polymerase chain reaction coupled with restriction fragment length polymorphism. RESULTS: Significant differences for the IL-6 (-572G/C) polymorphism were observed between patients with CD and controls (p=0.018, odds ratio (OR): 5.47, 95% confidence interval (CI): 1.161-25.800). No statistically significant association was observed between the IL-17 (-197A/G) polymorphism and CD (p>0.05). In addition, the symptoms and histopathological findings of children with CD were not related to either of the polymorphisms. CONCLUSION: The results of our study indicate that the IL-6 (-572G/C) polymorphism may play a role in susceptibility to CD.

Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease.

Development of the human nervous system involves complex interactions among fundamental cellular processes and requires a multitude of genes, many of which remain to be associated with human disease. We applied whole exome sequencing to 128 mostly consanguineous families with neurogenetic disorders that often included brain malformations. Rare variant analyses for both single nucleotide variant (SNV) and copy number variant (CNV) alleles allowed for identification of 45 novel variants in 43 known disease genes, 41 candidate genes, and CNVs in 10 families, with an overall potential molecular cause identified in >85% of families studied. Among the candidate genes identified, we found PRUNE, VARS, and DHX37 in multiple families and homozygous loss-of-function variants in AGBL2, SLC18A2, SMARCA1, UBQLN1, and CPLX1. Neuroimaging and in silico analysis of functional and expression proximity between candidate and known disease genes allowed for further understanding of genetic networks underlying specific types of brain malformations.

A novel insertion mutation identified in exon 10 of the MEFV gene associated with Familial Mediterranean Fever.

BACKGROUND: Familial Mediterranean Fever (FMF), characterized by recurrent fever and inflammation of serous membranes, is an autosomal recessive disease caused by mutations in the Mediterranean fever (MEFV) gene. Around 296 mutations have been reported to date. METHODS: Two two-generation Turkish families with a total of four members diagnosed with FMF clinically were screened with DNA sequencing performed on exon 2 and exon 10 of the MEFV genes. Then, complete exome sequencing analysis of MEFV gene was done for four patients in whom novel mutation was detected. RESULTS: A novel single base Guanine (G) insertion mutation in the coding region of MEFV gene, named c.2330dupG (p.Gln778Serfs*4 or Q778SfsX4) resulting in a mutated Pyrin/Marenostrin protein was identified. CONCLUSIONS: This is the first report of a new mutation in exon 10 of the MEFV gene in two Turkish families. This novel pattern of insertion mutation may provide important information for further studies on FMF pathogenesis.

Phototherapy causes a transient DNA damage in jaundiced newborns.

In this study, we aimed to clarify the following questions: 1) Does phototherapy (PT) cause genotoxicity in full-term newborn babies undergoing PT as a result of neonatal jaundice?, 2) if genotoxic effect occurs, is there any relationship between the duration of PT and genotoxicity?, and 3) is genotoxic effect temporary or not? The frequency of sister chromatid exchange (SCE) was determined in jaundiced newborns before, during, and after phototherapy, then determined again in childhood (approximately 3.5 years old). Mean frequency of SCE of 22 full-term jaundiced babies significantly increased during the PT procedure and in every single day, compared to the previous day, in comparison to the pre-PT basal value (6.20 ± 0.57;); mean SCE frequencies at 24, 48, 72, and 96 hours were 7.75 ± 0.40, 8.16 ± 0.47, 8.50 ± 0.40, and 9.36 ± 0.55, respectively (all P-values <0.01). In childhood, no significant difference was found between the mean SCE value (4.9 ± 0.9) of 20 of 22 children, who received PT in the neonatal period, and the mean SCE value (4.7 ± 0.6) of 20 coevaluated healthy children (P = 0.40). This study demonstrates that the negative effect of PT on SCE is a temporary effect.

The evaluation of genotoxic potential of ornidazole, nitroimidazole, in lymphocyte culture of patients with amebiasis.

The genotoxicity study of ornidazole (ONZ) was carried out on human lymphocyte chromosomes, using sister chromatid exchange (SCE) and micronucleus (MN). Thirty-two patients with Entemoeba histolitica infection who received 1000 mg/day for 10 days were included in this study. SCE and MN were measured before and after therapy. A statistically significant increase was observed in the SCE (P < 0.001) and MN frequencies (P < 0.001) after ornidazole therapy. It was concluded that ONZ has a potential geno- and cytotoxic effect in human peripheral lymphocyte cultures. For this reason, further, detailed studies are needed to elucidate the ONZ mechanism of genotoxicity and its carcinogenic potential.

CEP152 is a genome maintenance protein disrupted in Seckel syndrome.

Functional impairment of DNA damage response pathways leads to increased genomic instability. Here we describe the centrosomal protein CEP152 as a new regulator of genomic integrity and cellular response to DNA damage. Using homozygosity mapping and exome sequencing, we identified CEP152 mutations in Seckel syndrome and showed that impaired CEP152 function leads to accumulation of genomic defects resulting from replicative stress through enhanced activation of ATM signaling and increased H2AX phosphorylation.

HLA class I and class II genotyping in patients with chronic urticaria.

OBJECTIVES: Chronic urticaria (CU) is a common disease in which pathogenesis is unclear and which is resistant to therapy. Recent investigations have indicated that autoimmunity plays a role in nearly one third of CU patients. The present study aimed to investigate the relationship between human leukocyte antigen (HLA) class I and class II antigens and immune pathogenesis of CU. METHODS: HLA class I and class II antigens were investigated in 40 patients diagnosed with CU, utilizing serologic techniques and polymerase chain reactions. The study was performed between October 2005 and May 2006. Further HLA typing in patient subsets was done depending on the response of patients to intradermal injection of autologous serum. About 30 healthy and genetically unrelated individuals formed the control group for evaluation. RESULTS: The results revealed that HLA-B44 frequency was significantly higher (25%) in the patient group as compared with the matched control group (3.33%) (p = 0.033, OR = 9.667). There was no significant difference in HLA-A allelic distribution between the patient and control groups. In the genotyping of class II HLA alleles, HLA-DRB1*01 (25%) (p = 0.033, OR = 9.667) and HLA-DRB*15 (25%) (p = 0.033, OR = 9.667) were predominant alleles in the patient group. CONCLUSION: The association of HLA-B44, HLA-DRB1*01 and HLA-DRB*15 alleles with idiopathic CU suggests that there is a genetic component in the pathogenesis of CU.

Association of HLA class I and class II alleles with psoriasis vulgaris in Turkish population. Influence of type I and II psoriasis.

OBJECTIVE: To investigate the role of human leukocyte antigen (HLA) in susceptibility to psoriasis vulgaris in the Northeast region of Turkey and to contribute to the data related to HLA and psoriasis. METHODS: The study included 72 unrelated psoriatic patients (43 men and 29 women; aged 11-76 years) admitted to the Dermatology Department, University Research Hospital, Erzurum, Turkey between April 2002 and November 2003. We studied the distribution of HLA class I and II antigens in patients with psoriasis: 72 patients were divided into 2 groups according to the onset of psoriasis before age 40 years with family history (type I) and onset after age 40 without family history (type II). The HLA class I and II antigens were analyzed using the PCR-SSP method in 72 patients and in 104 controls. RESULTS: We found an increase in HLA-A*30 and A*68, B*7, B*13, B*57, Cw6, and DRB1*07 antigens in psoriatic patients compared with controls. As we compared type I and type II psoriasis with control group, B*57, Cw6 and DRB1*07 alleles were more significant in patients with type I psoriasis. Our patients with type II psoriasis represented a significant association with the HLA-B*13. CONCLUSION: Our findings along with previous HLA studies on psoriasis vulgaris patients from different racial groups showed that HLA-B*57 and DRB1*07 alleles are associated with the disease.

Genotoxicity of thallium-201 in patients with angina pectoris undergoing myocardial perfusion study.

Thallium-201 (201Tl) has been widely used as a nuclear reagent for myocardial blood flow imaging. The purpose of this study was to investigate genotoxic effects of 201Tl in patients with angina pectoris (n = 21), who had undergone myocardial perfusion imaging. Lymphocytes were isolated from each patient before, and 3, 30 and 90 days after 201Tl administration (111 MBq, 3 mCi) and were analyzed for chromosomal aberrations, sister chromatid exchanges, mitotic index and replicative index. There were significant increases in chromosomal aberrations and sister chromatid exchanges 3 days after 201Tl administration (p < 0.001), although no difference was noted in these values after 30 and 90 days (p > 0.05). Moreover, decreased mitotic index and replicative index were noted after 3 days of 201Tl administration (p < 0.001). These results suggest that the administration of 201Tl for myocardial blood flow imaging may induce genetic damage.

The assessment of genotoxic effects in lymphocyte cultures of infants treated with chloral hydrate.

Chloral hydrate is a sedative commonly used in pediatric medicine. It was evaluated for genotoxicity in cultured peripheral blood lymphocytes of infants who were given chloral hydrate for sedation. Sister chromatid exchange and micronucleus frequencies were determined before and after chloral hydrate administration. After treatment, the frequencies of sister chromatid exchange and micronuclei were significantly increased, suggesting that chloral hydrate has moderate genotoxic potential in infants.