A novel compound heterozygote mutation in the ARSB gene in a patient with Maroteaux-Lamy syndrome and its Insilico evaluation

Background: Maroteaux-Lamy syndrome (Mucopolysaccharidosis VI (MPS VI)) is a rare autosomal recessive disorder resulted from a deficiency in N-acetylgalactosamine 4-sulfatase (Arylsulfatase B, ASB). The enzyme deficiency leads to accumulation of Dermatan sulfate (DS) in connective tissue which causes phenotypes related to MPS VI. Over 145 disease-causing mutations in the ARSB gene have been identified and reported in the Human Gene Mutation Database (http://www.hgmd.cf.ac.uk/ac/index.php April 2018). This study aimed to characterize molecular and clinical features of a MPS VI patient who was the result of a consanguineous marriage and perform Insilico analysis of the mutated protein. Methods: In this study, we scanned the ARSB gene of an Afghan patient lived in Iran and previously confirmed as MPS VI by clinical examinations and enzymatic assay. We performed DNA extraction, polymerase chain reaction and direct sequencing on the entire coding region and exon-intron junctions. The structure of mutated enzyme was evaluated by Insilico analysis. Results: Two missense mutations were found in exon six (c.1178A > G (p.H393R) c.1210C > G (p.P404A) which predicted to be disease causing. Conclusion: These findings implicate the compound heterozygote mutation in ARSB gene and could be important for prenatal diagnosis. This is the first study and the first compound heterozygote that we report in this region of Asia. © 201

SIPA1L2, MIR4697, GCH1 and VPS13C loci and risk of Parkinson's diseases in Iranian population: A case-control study

Parkinson's disease (PD) is the second most common neurodegenerative disorder. Prevalence of PD increases steadily with age. A recent meta-analysis of genome-wide association studies has identified six new loci to be linked with PD. Here we investigated the association of four of these new loci, SIPA1L2, MIR4697, GCH1 and VPS13C with PD in an Iranian population. Through a case-control study a total of 1800 subjects comprising 600 PD patients and 1200 unrelated healthy controls were recruited. Rs10797576, rs329648, rs11158026 and rs2414739 related to SIPA1L2, MIR4697, GCH1 and VPS13C loci respectively, were genotyped in all subjects. The difference of genotype and allele frequencies between case and control groups were investigated using chi-square test and logistic regression models with R software. Genotype and allele frequencies were significantly different in PD patients and control group for rs329648, rs11158026 and rs2414739 (p-value = 0.018, 0.025, and 0.009 respectively for allele frequency differences). There was no difference in genotype nor allele frequencies between the two groups for rs10797576. We replicated the association of three new loci which are proposed for PD. More studies in other populations and also functional analysis are required to clear the role of these variants in PD. © 2016 Elsevier B.V

RIT2 Polymorphisms: Is There a Differential Association?

Neurological disorders include a wide variety of mostly multifactorial diseases related to the development, survival, and function of the neuron cells. Single-nucleotide polymorphisms (SNPs) have been extensively studied in neurological disorders, and in a number of instances have been reproducibly linked to disease as risk factors. The RIT2 gene has been recently shown to be associated with a number of neurological disorders, such as Parkinson’s disease (PD) and autism. In the study reported here, we investigated the association of the rs12456492 and rs16976358 SNPs of the RIT2 gene with PD, essential tremor (ET), autism, schizophrenia (SCZ), and bipolar disorder (BPD; total of 2290 patients), and 1000 controls, by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Significant association was observed between rs12456492 and two disorders, PD and ET, whereas rs16976358 was found to be associated with autism, SCZ, and BPD. Our findings are indicative of differential association between the RIT2 SNPs and different neurological disorders. © 2016, Springer Science+Business Media New York