Epidemiology and Genetics of Mucopolysaccharidosis Type VI in Russia.

Elena Voskoboeva,Ekaterina Zakharova,Sergey Kutsev,Natalia Pichkur,Olga Omzar,Galina Baydakova,Nato Vashakmadze,Svetlana Mikhaylova,Ochir Miklyaev,Amina Gamzatova,Alla Semyachkina

doi:10.3389/fmolb.2021.780184

Abstract

Mucopolysaccharidosis VI (MPS VI) is an autosomal recessive lysosomal storage disease caused by mutations in the arylsulfatase B gene (ARSB) and consequent deficient activity of ARSB, a lysosomal enzyme involved in the glycosaminoglycan (s) (GAGs) metabolism. Here, we present the results of the study of ARSB DNA analysis in MPS VI patients in the Russian Federation (RF) and other republics of the Former Soviet Union. In a cohort of 68 patients (57 families) with MPS VI, a total of 28 different pathogenic alleles were found. The most prevalent nucleotide changes included NM_000046.5:c.194C>T and NM_000046.5:c.454C>T. Five pathogenic alleles were novel, not previously reported (NM_000046.5:c.304C>G, NM_000046.5:c.533A>G, NM_000046.5:c.941T>C, NM_000046.5:c.447_456del10, and NM_000046.5:c.990_10003del14). The nucleotide variant NM_000045.6:c.454C>T was the prevalent allele among Slavic Russian patients. The nucleotide variant NM_000045.6:c.194C>T was found only in MPS VI families from the Republic of Dagestan. Based on the analysis of dry blood spots (DBSs) collected from newborns in this RF region, we showed the frequency of this mutant allele in the Republic of Dagestan to be 0.01 corresponding to the MPS VI frequency of nearly 1:10,000, which is one of the highest worldwide. This may eventually make the selective asymptomatic carrier test and newborn screening highly feasible in this region of the country.

Highlights

Mucopolysaccharidosis VI (MPS VI, OMIM: 253200) is a rare autosomal recessive lysosomal storage disorder (LSD) caused by mutations in the arylsulfatase B gene (ARSB) located on chromosome 5 (5q13–5q14) (Karageorgos et al, 2007)
Based on the analysis of dry blood spots (DBSs) collected from newborns in this Russian Federation (RF) region, we showed the frequency of this mutant allele in the Republic of Dagestan to be 0.01 corresponding to the MPS VI frequency of nearly 1:10,000, which is one of the highest worldwide
Pathogenic nucleotide variants in this gene result in reduced activity of arylsulfatase B (ASB, N-acetyl-galactosamine-4sulfatase, EC 3.1.6.12), an enzyme required for the degradation of the glycosaminoglycans (GAGs) dermatan sulfate (DS) and chondroitin 4-sulfate (C4S)

Summary

Introduction

Mucopolysaccharidosis VI (MPS VI, OMIM: 253200) is a rare autosomal recessive lysosomal storage disorder (LSD) caused by mutations in the arylsulfatase B gene (ARSB) located on chromosome 5 (5q13–5q14) (Karageorgos et al, 2007). Dermatan sulfate is found in the connective tissue of various organs, the skin, tendons, blood vessels, and the respiratory tract, but mainly in heart valves. The accumulation of dermatan sulfate in lysosomes leads to irreversible cell damage and organ dysfunction. In Brazil, Portugal, and British Columbia, the frequency of MPS VI is high in comparison to other MPSs. In Australia and Tunisia, the incidence of MPSVI is higher than that in other countries (Khan et al, 2017)

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