Worldwide distribution of common <i>IDUA</i> pathogenic variants

Poletto, Édina; Pasqualim, Gabriela; Giugliani, Roberto; Matte, Úrsula; Baldo, Guilherme

doi:10.1111/cge.13224

Cited by 39 publications

(57 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The second phase of the study consisted of the investigation of “healthy” volunteers to estimate the frequency of heterozygotes for the pathogenic variant most commonly found by MBN and according to Poletto et al, in MPS I: IDUA p.Trp402Ter (W402X). To this end, adult blood donors from the Hospital de Clínicas de Porto Alegre (HCPA) Blood Bank were invited to participate from December 2015 to November 2016.…”

Section: Methodsmentioning

confidence: 99%

Estimated birth prevalence of mucopolysaccharidoses in Brazil

Federhen

Pasqualim

Freitas

et al. 2020

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Several studies have been published on the frequency of the mucopolysaccharidoses (MPS) in different countries. The objective of the present study was to estimate the birth prevalence (BP) of MPS in Brazil. MPS diagnosis registered at MPS‐Brazil Network and in Instituto Vidas Raras were reviewed. BP was estimated by (a) the number of registered patients born between 1994 and 2015 was divided by the number of live births (LBs), and (b) a sample of 1,000 healthy individuals was tested for the most frequent variant in IDUA gene in MPS I (p.Trp402Ter) to estimate the frequency of heterozygosity and homozygosity. (a) The BP based on total number of LBs was (cases per 100,000 LBs): MPS overall: 1.25; MPS I: 0.24; MPS II: 0.37; MPS III: 0.21; MPS IV: 0.14; MPS VI: 0.28; MPS VII: 0.02. (b) The overall frequency of p.Trp402Ter was 0.002. Considering the frequency of heterozygotes for the p.Trp402Ter IDUA variant in the RS state, the frequency of this variant among MPS I patients and the relative frequency of the different MPSs, we estimated the birth prevalence of MPS in total and of each MPS type, as follows: MPS overall: 4.62; MPS I: 0.95; MPS II: 1.32; MPS III: 0.56; MPS IV: 0.57; MPS VI: 1.02; MPS VII: 0.05. This study provided original data about BP and relative frequency of the MPS types, in Brazil, based on the frequency of the commonest IDUA pathogenic variant and in the records of two large patient databases.

show abstract

Section: Methodsmentioning

confidence: 99%

Estimated birth prevalence of mucopolysaccharidoses in Brazil

Federhen

Pasqualim

Freitas

et al. 2020

American J of Med Genetics Pt A

View full text Add to dashboard Cite

show abstract

“…7 Over 200 pathogenic IDUA variants have been reported to underlie MPS I and a genotype-phenotype association is emerging whereby patients who are either homozygous or compound heterozygous for the common nonsense mutations W402X or Q70X consistently have severe disease. [14][15][16][17][18][19] The large number of patients enrolled in the MPS I Registry offers a unique resource for further elaboration of genotype/phenotype relationships for this rare disease. [20][21][22] 2 | MATERIALS AND METHODS…”

Section: Introductionmentioning

confidence: 99%

Genotype‐phenotype relationships in mucopolysaccharidosis type I (MPS I): Insights from the International MPS I Registry

et al. 2019

View full text Add to dashboard Cite

Mucopolysaccharidosis type I (MPS I) is a rare autosomal recessive disorder resulting from pathogenic variants in the α‐L‐iduronidase (IDUA) gene. Clinical phenotypes range from severe (Hurler syndrome) to attenuated (Hurler‐Scheie and Scheie syndromes) and vary in age of onset, severity, and rate of progression. Defining the phenotype at diagnosis is essential for disease management. To date, no systematic analysis of genotype‐phenotype correlation in large MPS I cohorts have been performed. Understanding genotype‐phenotype is critical now that newborn screening for MPS I is being implemented. Data from 538 patients from the MPS I Registry (380 severe, 158 attenuated) who had 2 IDUA alleles identified were examined. In the 1076 alleles identified, 148 pathogenic variants were reported; of those, 75 were unique. Of the 538 genotypes, 147 (27%) were unique; 40% of patients with attenuated and 22% of patients with severe MPS I had unique genotypes. About 67.6% of severe patients had genotypes where both variants identified are predicted to severely disrupt protein/gene function and 96.1% of attenuated patients had at least one missense or intronic variant. This dataset illustrates a close genotype/phenotype correlation in MPS I but the presence of unique IDUA missense variants remains a challenge for disease prediction.

show abstract

“…1 The progressive accumulation of DS and HS in lysosomes results in the severe decline of cells, tissues, and organs. 7 The influence of mutations on IDUA enzyme activity has broad variability, and thus, IDUA is provided in different forms; however, there is not a significant relationship between the IDUA genotypes and various phenotypes that are observed in MPSI. 2 MPSI is considered to be one of the most commonly lysosomal storage disorders in different populations with a mean incidence of 1:100 000-1:150 000 newborns.…”

Section: Introductionmentioning

confidence: 99%

“…The IDUA mutations, p.Trp402ter (rs121965019) and p.Pro533Arg (rs121965021), have been already reported to account for more than 50% of MPSI alleles in most populations. 7 The influence of mutations on IDUA enzyme activity has broad variability, and thus, IDUA is provided in different forms; however, there is not a significant relationship between the IDUA genotypes and various phenotypes that are observed in MPSI. In addition, there is no proved significance relationship in studies published elsewhere between residual l-iduronidase levels and MPSI phenotype.…”

Section: Introductionmentioning

confidence: 99%

Mutation analysis and clinical characterization of Iranian patients with mucopolysaccharidosis type I

Taghikhani

Khatami

Abdi

et al. 2019

Clinical Laboratory Analysis

View full text Add to dashboard Cite

BackgroundMucopolysaccharidosis type I (MPSI) is a rare autosomal recessive disorder caused by a deficiency of α‐l‐iduronidase (IDUA) encoded by the IDUA gene. We examined the mutation spectrum of the IDUA gene to explain the clinical, biochemical, and molecular features in 21 Iranian patients with MPSI.MethodsSanger sequencing was used to measure the IDUA gene sequence in the coding region and exon‐intron boundaries. We recorded the clinical findings of studied patients at the first diagnosis of disease and then during the treatment and follow‐up.ResultsFive different missense disease‐causing mutations were determined in our patient groups, indicating 90.48% of detection rate. The most widespread mutation was the p.Y109H, occurring in 15.625% of all alleles, which was reported for the first time in our study. Other frequent mutations were as follows: p.Ser157Pro (12.5%), p.Gly84Arg (12.5%), p.Asp257His (9.375%), and p.Asp301Glu (9.375%). Three ones of them were new missense mutations: p.Ser157Pro, p.Asp257His, and p.Asp301Glu.DiscussionThe results of this study explain the different spectrum of IDUA gene mutations in our patients with MPSI. We introduced here 32 different variants including four new variants: p.Y109H (15.625%), p.S157P (12.5%), p.D257H (9.375%), and p.D301E (9.375%). In this series, there was no relationship between the happening of clinical features and genotype variations and biochemical findings.

show abstract

Worldwide distribution of common IDUA pathogenic variants

Cited by 39 publications

References 71 publications

Estimated birth prevalence of mucopolysaccharidoses in Brazil

Estimated birth prevalence of mucopolysaccharidoses in Brazil

Genotype‐phenotype relationships in mucopolysaccharidosis type I (MPS I): Insights from the International MPS I Registry

Mutation analysis and clinical characterization of Iranian patients with mucopolysaccharidosis type I

Contact Info

Product

Resources

About