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Introduction: Mucopolysaccharidoses are a group of lysosomal storage disorders that include seven types that are classified based on the enzymes that are disrupted. Malfunction of these enzymes leads to the accumulation of glycosaminoglycans (GAGs) in various tissues. Due to genetic and clinical heterogeneity, diagnosing and distinguishing the different types is challenging. Genetic methods such as whole exome sequencing (WES) and Sanger sequencing are accurate methods for detecting pathogenic variants in patients. Methods: Thirty-two cases of mucopolysaccharidosis, predominantly from families with consanguineous marriages, were genetically examined. Out of these, fourteen cases underwent targeted sequencing, while the rest underwent WES. The results of WES were analyzed and the pathogenicity of the variants was examined using bioinformatics tools. In addition, a segregation analysis within families was carried out. Results: In most cases, a pathogenic or likely pathogenic variant was detected. Sixteen previously reported variants and six new variants were detected in the known IDS (c.458G>C, c.701del, c.920T>G), GNS (c.1430A>T), GALNS (c.1218_1221dup), and SGSH (c.149T>C) genes. Furthermore, we discovered a c.259G>C substitution in the NAGLU gene for the first time in three homozygous patients. This substitution was previously reported as heterozygous. Except for the variants related to the IDS gene, which were hemizygous, all the other variants were homozygous. Discussion: It appears that the high rate of consanguineous marriages in the families being studied has had a significant impact on the occurrence of this disease. Overall, these findings could expand the spectrum of pathogenic variants in mucopolysaccharidoses. Genetic methods, especially WES, are very accurate and can be used alone or in conjunction with other diagnostic methods for a more precise and rapid diagnosis of mucopolysaccharidoses. Additionally, they could be beneficial for family screening and disease prevention.
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OBJECTIVE: Multiple sclerosis (MS) is a partially heritable autoimmune disease. HLA-DR2 is the largest identified genetic risk factor for MS. The largest identified genetic risk factor is haplotype from the MHC class II HLA-DR2, which increases the disease risk. The HLA-DR2 distribution in MS patients has been confirmed, but contradictory outcomes have been found. Moreover, the HLA-DR2 effect on ethnicity and gender is unclear. There are no data regarding the HLA-DR2 (HLA-DRB1*1501-DRB5*01-DQB1*0602) association with MS in Khuzestan Province, Iran. This study aimed to investigate the association of HLA-DR2 with MS regarding both sex and ethnicity in this province. MATERIALS & METHODS: A total of 399 individuals were recruited. HLA typing was conducted using the polymerase chain reaction amplification with sequence-specific primers technology. The HLA-DR2 association with MS was analyzed, and also its probable association with gender, ethnicity, the expanded disability status scale (EDSS), and MS clinical course was examined using the Chi-square test. RESULTS: HLA-DRB5*01 - -DQB1*0602 - as the most common HLA haplotype was found in both patient and control groups. In contrast, the DRB5*01 + -DRB1*1501 + -DQB1*0602 - frequency was very low in the groups. It was observed that haplotypes had no association with MS susceptibility. Most of the haplotypes showed no association with ethnicity, sex, EDSS, and MS course except for the HLA-DRB5*01 + -DRB1*1501 + -DQB1*0602 - haplotype that was positively associated with EDSS steps 5 to 10 (p=0.014) and non-RRMS (p=0.023). CONCLUSION: There was no association between HLA-DR2 and MS susceptibility. However, the higher HLA-DRB5*01 + -DRB1*1501 + -DQB1*0602 - frequency may play a role in MS development. Also, HLA-DR2 did not increase significantly concerning clinical course, ethnicity, sex, and EDSS. This study further supports the importance of replication studies as susceptible loci that might differ in various ethnicities. Therefore, it is concluded that the association between HLA-DR2 and MS is more allelic than haplotypic in Khuzestan.
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BACKGROUND: Multiple sclerosis (MS) is a chronic, demyelinating, autoimmune and also complex disease of the central nervous system the etiology of which is not completely defined; but both genetic and environmental factors are regarded as main factors in its susceptibility. HLA-DQB1*0602 is considered as one of the most important genetic factors in MS predisposition but contradictory results have been reported in different populations world-wide. Since there are no data with respect to the correlation of HLA-DQB1*0602 and multiple sclerosis in Khuzestan province, and because of ethnic diversity in Khuzestan province, the aim was to examine the association of this allele with multiple sclerosis in Khuzestan. METHODS: This is a case control study that evaluated 200 MS patients from Khuzestan and 200 healthy individuals from the same geographical region. DNA extraction was performed by salting out method; in addition, HLA typing was carried out by polymerase chain reaction amplification with sequence-specific primers (PCR-SSP) method. The present study also considered probable association among HLA-DQB1*0602 with sex, ethnicity, and type of disease. RESULTS: Results revealed that distribution of mentioned allele was not statistically different among cases and controls (61.5% vs. 64%, P = 0.605); furthermore, no association was shown between this allele and gender, ethnicity or type of disease. CONCLUSION: On the whole, our result is consistent with most of the other studies in Iran; but contrasts with most of the studies in European populations.
