Identification of a novel compound heterozygous mutation in BBS12 in an Iranian family with bardet-biedl syndrome using targeted next generation sequencing

Bardet-Biedl syndrome [BBS] is a pleiotropic and multisystemic disorder characterized by rod-cone dystrophy, polydactyly, learning difficulties, renal abnormalities, obesity and hypogonadism. This disorder is genetically heterogeneous. Until now, a total of nineteen genes have been identified for BBS whose mutations explain more than 80% of diagnosed cases. Recently, the development of next generation sequencing [NGS] technology has accelerated mutation screening of target genes, resulting in lower cost and less time consumption. Here, we screened the most common BBS genes [BBS1-BBS13] using NGS in an Iranian family of a proposita displaying symptoms of BBS. Among the 18 mutations identified in the proposita, one [BBS12 c.56T>G and BBS12 c.1156C>T] was novel. This compound heterozygosity was confirmed by Sanger sequencing in the proposita and her parents. Although our data were presented as a case report, however, we suggest a new probable genetic mechanism other than the conventional autosomal recessive inheritance of BBS. Additionally, given that in some Iranian provinces, like Khuzestan, consanguineous marriages are common, designing mutational panels for genetic diseases is strongly recommended, especially for those with an autosomal recessive inheritance pattern

Association study between coronary artery disease and rs1333049 and RS10757274 polymorphisms at 9P21 locus in south-west Iran

Coronary artery disease [CAD] is a multi-factorial and heterogenic disease with atherosclerosis plaques formation in internal wall of coronary artery. Plaque formation results to limitation of the blood reaching to myocardium leading to appearance of some problems, such as ischemia, sudden thrombosis veins and myocardial infarction [MI]. Several environmental and genetic factors are involved in prevalence and incident of CAD as follows: hypertension, high low density lipoprotein-cholesterol [LDL-C], age, diabetes mellitus, family history of early-onset heart disease and smoking. According to genome wide association studies [GWAS], five polymorphisms in the 9p21 locus seem to be associated with the CAD. We aimed to evaluate the remarkable association of two polymorphisms at 9p21 locus, rs1333049 and rs10757274, with CAD. This experimental study was conducted in Golestan, Aria Hospitals and Genetics Lab of Shahid Chamran University in the city of Ahvaz, Iran, in 2010- 2011. The collected blood samples belonging to 170 CAD patients [case group] and 100 healthy individuals [control group] were analyzed by tetra-primer amplification refractory mutation system [ARMS]-polymerase chain reaction [PCR] technique. The results were analyzed using software package used for statistical analysis [SPSS; SPSS Inc., USA] version 16. A value of p<0.05 and an odd ratio [OR] with 95% confidence intervals [CI] were considered significant. The frequencies of CC, CG and GG genotypes for rs1333049 polymorphism in patients were 18.2, 65.3 and 16.5%, while in controls, the related values were 25, 67 and 8%, respectively. GG genotypes of rs1333049 polymorphism in CAD patients were more than control cases [OR: 0.354, 95%CI: 0.138-0.912, p=0.032]. The frequencies of AA, AG and GG genotypes for rs10757274 in CAD patients were 8.2, 58.3 and 33.5%, while in controls, the related values were 35, 63 and 2%, respectively. GG Genotype in rs10757274 polymorphism in CAD patients was found more than control cases [OR: 0.014, 95% CI: 0.003 -0.065, p=0.0001]. The rs1333049 polymorphism at 9p21 locus shows a weak association with CAD, whereas rs10757274 polymorphism reveals a significant association with CAD. These variants may help the identification of patients with increased risk for coronary artery disease