Mutational analysis of ARSB gene in mucopolysaccharidosis type VI: identification of three novel mutations in Iranian patients
محل انتشار: مجله علوم پایه پزشکی ایران، دوره: 21، شماره: 9
سال انتشار: 1397
نوع سند: مقاله ژورنالی
زبان: انگلیسی
مشاهده: 149
فایل این مقاله در 7 صفحه با فرمت PDF قابل دریافت می باشد
- صدور گواهی نمایه سازی
- من نویسنده این مقاله هستم
استخراج به نرم افزارهای پژوهشی:
شناسه ملی سند علمی:
JR_IJBMS-21-9_012
تاریخ نمایه سازی: 27 مهر 1400
چکیده مقاله:
Objective(s): Mucopolysaccharidosis VI (MPS VI) or Maroteaux-Lamy syndrome is a rare metabolic disorder, resulting from the deficient activity of the lysosomal enzyme arylsulfatase B (ARSB). The enzymatic defect of ARSB leads to progressive lysosomal storage disorder and accumulation of glycosaminoglycan (GAG) dermatan sulfate (DS), which causes harmful effects on various organs and tissues and short stature. To date, more than ۱۶۰ different mutations have been reported in the ARSB gene.Materials and Methods: Here, we analyzed ۴ Iranian and ۲ Afghan patients, with dysmorphism indicating MPS VI from North-east Iran. To validate the patients’ type of MPS VI, urine mucopolysaccharide and leukocyte ARSB activity were determined. Meanwhile, genomic DNA was amplified for all ۸ exons and flanking intron sequences of the ARSB gene to analyze the spectrum of mutations responsible for the disorder in all patients.Results: Abnormal excretion of DS and low leukocyte ARSB activity were observed in the urine samples of all ۶ studied patients. In direct DNA sequencing, we detected four different homozygous mutations in different exons, three of which seem not to have been reported previously: p.H۱۷۸N, p.H۲۴۲R, and p.*۵۳۴W. All three novel substitutions were found in patients with Iranian breed. We further detected the IVS۵+۲T>C mutation in Afghan siblings and four different homozygous polymorphisms, which have all been observed in other populations. Conclusion: results indicated that missense mutations were the most common mutations in the ARSB gene, most of them being distributed throughout the ARSB gene and restricted to individual families, reflecting consanguineous marriages.
کلیدواژه ها:
ARSB gene ، Arylsulfatase B ، Consanguineous marriage ، DNA sequencing ، Maroteaux-Lamy syndrome ، Mucopolysaccharidosis VI (MPS VI)
نویسندگان
Nasrin Malekpour
Department of Human Genetics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Islamic Republic of Iran
Rahim Vakili
Division of Endocrinology and Metabolism, Department of Pediatrics, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Islamic Republic of Iran
Tayebeh Hamzehloie
Department of Human Genetics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Islamic Republic of Iran
مراجع و منابع این مقاله:
لیست زیر مراجع و منابع استفاده شده در این مقاله را نمایش می دهد. این مراجع به صورت کاملا ماشینی و بر اساس هوش مصنوعی استخراج شده اند و لذا ممکن است دارای اشکالاتی باشند که به مرور زمان دقت استخراج این محتوا افزایش می یابد. مراجعی که مقالات مربوط به آنها در سیویلیکا نمایه شده و پیدا شده اند، به خود مقاله لینک شده اند :