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.

Waardenburg syndrome type 2A in a large Iranian family with a novel MITF gene mutation.

BACKGROUND: The characteristics of Waardenburg syndrome (WS) as a scarce heritable disorder are sensorineural hearing loss and deficits of pigmentation in the skin, hair, and eye. Here, clinical features and detection of the mutation in the MITF gene of WS2 patients are reported in a sizable Iranian family. METHODS: A man aged 28-years represented with symptoms of mild unilateral hearing loss (right ear), complete heterochromia iridis, premature graying prior to 30 years of age, and synophrys. In this research, there was a sizable family in Iran comprising three generations with seven WS patients and two healthy members. Whole exome sequencing was applied for proband for the identification of the candidate genetic mutations associated with the disease. The detected mutation in proband and investigated family members was validated by PCR-Sanger sequencing. RESULTS: A novel heterozygous mutation, NM_198159.3:c.1026dup p.(Asn343Glufs*27), in exon 9 of the MITF gene co-segregated with WS2 in the affected family members. The variant was forecasted as a disease-causing variant by the Mutation Taster. According to the UniProt database, this variant has been located in basic helix-loop-helix (bHLH) domain of the protein with critical role in DNA binding. CONCLUSIONS: A frameshift was caused by a nucleotide insertion, c.1026dup, in exon 9 of the MITF gene. This mutation is able to induce an early termination, resulting in forming a truncated protein capable of affecting the normal function of the MITF protein. Helpful information is provided through an exactly described mutations involved in WS to clarify the molecular cause of clinical characteristics of WS and have a contribution to better genetic counseling of WS patients.

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.

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.