Mucopolysaccharidosis Type I in the Russian Federation and Other Republics of the Former Soviet Union: Molecular Genetic Analysis and Epidemiology

Abstract

Mutations in the IDUA gene cause deficiency of the lysosomal enzyme alpha-l-iduronidase (IDUA), which leads to a rare disease known as mucopolysaccharidosis type I. More than 300 pathogenic variants of the IDUA gene have been reported to date, but not much is known about the distribution of mutations in different populations and ethnic groups due to the low prevalence of the disease. This article presents the results of a molecular genetic study of 206 patients with mucopolysaccharidosis type I (MPS I) from the Russian Federation (RF) and other republics of the former Soviet Union. Among them, there were 173 Russian (Slavic) patients, 9 Tatars, and 24 patients of different nationalities from other republics of the former Soviet Union. Seventy-three different pathogenic variants in the IDUA gene were identified. The common variant NM_000203.5:c.208C>T was the most prevalent mutant allele among Russian and Tatar patients. The common variant NM_000203.5:c.1205G>A accounted for only 5.8% mutant alleles in Russian patients. Both mutations were very rare or absent in patients from other populations. The pathogenic variant NM_000203.5:c.187C>T was the major allele in patients of Turkic origin (Altaian, Uzbeks, and Kyrgyz). Specific own pathogenic alleles in the IDUA gene were identified in each of these ethnic groups. The identified features are important for understanding the molecular origin of the disease, predicting the risk of its development and creating optimal diagnostic and treatment tools for specific regions and ethnic groups.

A Novel IDUA Mutation Causing Ocular Disease in 2 Siblings

“…Missense/nonsense mutations accounted for the highest proportion, other mutation types were splice site mutations, deletions, and insertions, and complex rearrangements. 9 However, the association between genotype and phenotype is unclear due to differences in genetic polymorphism and environmental factors. Current treatment options for MPS I include hematopoietic stem cell transplantation (HSCT), enzyme replacement therapy (ERT), or a combination of both therapies.…”

Mucopolysaccharidosis Type I Presenting with Persistent Neonatal Respiratory Distress: A Case Report

“…There are currently thirteen MPSs that have been identified, and two of them were found in the 2020s [ 1 ]. Mucopolysaccharidosis type I (MPS I) is a rare inherited autosomal recessive lysosomal storage disorder caused by pathogenic α-L-iduronidase (IDUA) gene variant mutations, resulting in a deficiency of IDUA activity [ 1 , 2 ]. The IDUA gene has 14 exons and 13 introns and is found on chromosome 4 at location 4p16.3 [ 1 , 2 , 3 , 4 ].…”

“…Mucopolysaccharidosis type I (MPS I) is a rare inherited autosomal recessive lysosomal storage disorder caused by pathogenic α-L-iduronidase (IDUA) gene variant mutations, resulting in a deficiency of IDUA activity [ 1 , 2 ]. The IDUA gene has 14 exons and 13 introns and is found on chromosome 4 at location 4p16.3 [ 1 , 2 , 3 , 4 ]. There have been >300 reported variants of IDUA in the Human Genetic Mutation Database, the majority of which are missense/nonsense mutations [ 2 ].…”

“…The IDUA gene has 14 exons and 13 introns and is found on chromosome 4 at location 4p16.3 [ 1 , 2 , 3 , 4 ]. There have been >300 reported variants of IDUA in the Human Genetic Mutation Database, the majority of which are missense/nonsense mutations [ 2 ]. Several studies have reported that p.W402X, p.Q70X, p.P533R, and p.G51D are the most common IDUA disease-causing mutations [ 2 , 4 , 5 , 6 ].…”

MPSI Manifestations and Treatment Outcome: Skeletal Focus

“…Copy number variations have been also reported [ 10 ]. The most common causative variants reported worldwide include c.1205G > A (p.Trp402Ter), c.208C > T (p.Gln70Ter), c.1598C > G (p.Pro533Arg), and c.152G > A (p.Gly51Asp) [ 2 , 11 , 12 ]. c.1205G > A accounts for approximately 45% of disease alleles in the United States, whereas c.208C > T is mostly recorded in Russia and Scandinavia with a 50% frequency [ 2 , 13 , 14 , 15 ].…”