mohammad dehani

Bardet–Biedl Syndrome (BBS) is a rare pleiotropic autosomal recessive disease related to ciliopathies with approximately 25 causative genes. BBS is a multisystemic disorder with wide spectrum of manifestations including truncal obesity, retinal dystrophy, male hypogenitalism, postaxial polydactyly, learning difficulties, and renal abnormalities.

A consanguineous Iranian family with a 28-year-old daughter affected with BBS, resulting from a first cousin marriage, was examined. After clinical examination, Whole Exome Sequencing (WES) was applied. Following the analysis of exome data, Sanger sequencing was used to confirm as well as to co-segregate the candidate variant with the phenotype.

A novel homozygous variant [c. 2035G>A (p.E679K)] in exon 2 of the BBS10 gene was found which was categorized as likely pathogenic based on American College of Medical Genetics and Genomics (ACMG) guidelines and criteria. In this study, the variant was fully co-segregated with the phenotype in the family.

Despite overlapping with other ciliopathies in terms of the phenotype, the BBS has high genetic heterogeneity and clinical variability even among affected members of a family. The symptoms observed in patients are largely related to the genes involved and the type of mutations in the BBS. In this study, in addition to phenotype description of the proband harboring a novel disease-causing variant in BBS10 gene, the spectrum of BBS symptoms was expanded. The findings of this study can be useful in genetic counseling, especially for risk estimation and prenatal diagnosis.

MicroRNA-124 (miR-124) is known as an important regulator of the immune system and inflammatory response. Studies have reported that this miRNA is dysregulated in autoimmune disorders such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). A functional analysis demonstrated that rs531564 (C>G) affects the biogenesis of primary microRNA transcript-124 (pri-miR-124) and changes the expression of mature miR-124. In the present study, for the first time, we intended to evaluate the possible association between rs531564 polymorphism with SLE and RA risk.  In this case-control study, 110 patients with SLE, 115 patients with RA, and 120 healthy subjects were enrolled to evaluate rs531564 genotypes with real-time polymerase chain reaction (PCR) high resolution melting method. Our findings demonstrated that frequency of GC genotype and G allele were considerably higher in the control group than RA patients, demonstrating that that GC genotype and G allele have a protective effect for healthy individuals (GC vs CC; OR: 0.29; 95%CI [0.12,0.67] and G vs C; OR: 0.42; 95%CI [0.23,0.78]). However, no significant correlation was confirmed between allele and genotype frequencies of rs531564 with SLE risk (p>0.05). However, the G allele in rs531564 polymorphism was associated with serum level of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), anti-dsDNA antibody, C3, C4, and creatinine, and frequency of renal involvements in SLE patients (p<0.05). Moreover, in RA patients, the G was correlated with lower concentration ESR and CRP (p<0.001).  Our findings propose a considerable association between rs531564 polymorphism in the pri-miR-124 gene with susceptibility and clinical characteristics of RA and SLE in the Iranian population.