A novel frameshift mutation in the EDA gene in an Iranian patient affected by X-linked hypohidrotic ectodermal dysplasia.

PURPOSE: Ectodermal dysplasias are characterized by developmental abnormalities in ectodermal structures. Hypohidrotic ectodermal dysplasias (HED) are the most common subtype. They are most commonly inherited via X-linked recessive routes. We report on a novel ectodysplasin-A (EDA) mutation that is expected to be involved in pathogenesis of HED. METHODS: Hypohidrotic ectodermal dysplasia genes, including EDA, EDAR and EDARADD, were analyzed using next-generation sequencing (NGS). The detected mutation on the EDA gene was confirmed in the patient and his mother using Sanger sequencing. RESULTS: The patient presented with adontia, absence of gum development, hyperthermia and hypohidrosis. Our genetic analysis of the patient revealed a novel frameshift hemizygous mutation (c.898_924 + 8del35ins4CTTA) on the EDA gene. The patient's mother showed a mild HED phenotype. Direct sequencing of the EDA gene in the region where her son had the mutation showed the same mutation in a heterozygous state. CONCLUSION: We identified a novel frameshift mutation in the EDA gene in an Iranian patient affected by X-linked HED. The difference between our patient's symptoms and those recorded for some previous subjects may be due to the differences in the mutations involved.

Association of common genetic variants of KCNJ11 gene with the risk of type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a multifactorial polygenic disease. Potassium inwardly-rectifying channel, subfamily J, member 11 (KCNJ11) gene mutations can result in susceptibility of T2DM. The aim of this study is to investigate the relationship between risk of T2DM and its complications (retinopathy & renal) and polymorphisms rs5210 and rs5215 of the KCNJ11 gene in a group of Iranian population. In this case-control study, 111 Iranian patients with T2DM and 82 control subjects were genotyped for each polymorphism by polymerase chain reaction (PCR) and Sanger Sequencing methods. Frequencies of genotypes of rs5210 polymorphism among subjects with and without diabetes mellitus were 53.15% vs. 51.22% for GG and 37.84% vs. 42.68% for AG (p = 0.7), respectively. Corresponding frequencies for rs5215 polymorphism among diabetics and non-diabetics were 13.51% vs. 13.41% for CC and 50.45% vs. 37.80% for CT (p = 0.2). G allele carriers (rs5210 polymorphism) and C allele carriers (rs5215 polymorphism) had the same frequency among diabetics and non-diabetics (p = 0.9 for G allele and p = 0.2 for C allele). Our results suggested that none of the polymorphisms of KCNJ11, rs5210 (p = 0.7) and rs5215 (p = 0.2), were significantly associated with T2DM. Only, the relationship between CT genotype of rs5215 and retinopathy (p = 0.01) showed a borderline significant association.

A systematic review of miRNAs as biomarkers in osteoporosis disease.

BACKGROUND: Osteoporosis is often considered to be a disease of the elderly, which is characterized by two characteristics: low bone mineral density (BMD) and increased risk of fracture. MicroRNAs (miRNAs) have been reported to play a potential role in bone formation and resorption, bone remodeling, bone homeostasis regulation, and bone cell differentiation. Therefore, altered expression of different miRNAs may impact the pathology of bone diseases such as osteoporosis. A systematic review was conducted to extract all miRNA found to be significantly dys-regulated in the peripheral blood. METHODS: This review was carried out using a systematically search on PubMed, Scopus, Embase, Web of Science (WoS), and Cochrane databases from 1990 to 2018 to explore the diagnostic value of miRNAs as a biomarker in osteoporosis. RESULTS: A total of 31 studies were identified in the systematic review that indicated more than 30 kinds of up-regulated and down-regulated miRNAs in three categories; postmenopausal osteoporosis, postmenopausal osteoporosis with fracture risk, and other types of osteoporosis and fracture risk. CONCLUSION: The collective data presented in this review indicate that miRNAs could serve as biomarkers for the diagnosis (onset) and prognosis (progression of osteoporosis), while the clinical application of these findings has yet to be verified. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-021-00873-5.

PPARG (Pro12Ala) genetic variant and risk of T2DM: a systematic review and meta-analysis.

Type 2 diabetes mellitus (T2DM) is a complex disease caused by the interaction between genetic and environmental factors. A growing number of evidence suggests that the peroxisome proliferator-activated receptor gamma (PPARG) gene plays a major role in T2DM development. Meta-analysis of genetic association studies is an efficient tool to gain a better understanding of multifactorial diseases and potentially to provide valuable insights into gene-disease interactions. The present study was focused on assessing the association between Pro12Ala variation in the PPARG and T2DM risk through a comprehensive meta-analysis. We searched PubMed, WoS, Embase, Scopus and ProQuest from 1990 to 2017. The fixed-effect or random-effect model was used to evaluate the pooled odds ratios (ORs) and 95% confidence intervals (CIs) depending on the heterogeneity among studies. The sources of heterogeneity and publication bias among the included studies were assessed using I2 statistics and Egger's tests. A total of 73 studies, involving 62,250 cases and 69,613 controls were included. The results showed that the minor allele (G) of the rs1801282 variant was associated with the decreased risk of T2DM under different genetic models. Moreover, the protective effect of minor allele was detected to be significantly more in some ethnicities including the European (18%), East Asian (20%), and South East Asian (18%). And the reduction of T2DM risk in Ala12 carriers was stronger in individuals from North Europe rather than Central and South Europe. Our findings indicated that the rs1801282 variant may contribute to decrease of T2DM susceptibility in different ancestries.