Molecular Analysis of Turkish Maroteaux-Lamy Patients and Identification of One Novel Mutation in the Arylsulfatase B (ARSB) Gene

Zanetti, Alessandra; Önenli-Mungan, Neslihan; Elçioğlu, Nursel; Özbek, Mehmet Nuri; Kör, Deniz; Lenzini, Elisabetta; Scarpa, Maurizio; Tomanin, Rosella

doi:10.1007/8904_2013_276

Cited by 5 publications

(6 citation statements)

References 27 publications

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“…c.1036del was heavily represented in this population. Interestingly, p.(Leu321Pro) did not appear to be associated with a phenotypic signature in this population, possibly due to the relatively high rates of consanguineous marriages in Turkey, leading to a higher proportion of homozygous alleles across the genome and variable clinical phenotypes (Koc, ; Zanetti et al., ).…”

Section: Variantsmentioning

confidence: 85%

“…Interestingly, the c.962T>C mutation is not found in gnomAD (gnomad.broadinstitute.org, accessed October 26, 2017), further supporting the hypothesis that this is primarily a population‐specific variant. Individuals homozygous for p.(Leu321Pro) demonstrated a range of clinical phenotypes, from a classic, rapidly progressing phenotype to a non‐classical, slowly progressing phenotype (Isbrandt et al., ; Kantaputra et al., ; Zanetti et al., ). Of note, Leu321 is not conserved between the arylsulfatases, and the effect of the p.(Leu321Pro) mutation on the secondary structure of ASB is not known (Isbrandt et al., ).…”

Section: Variantsmentioning

confidence: 99%

“…Individuals homozygous for p.(Leu321Pro) demonstrated a range of clinical phenotypes, from a classic, rapidly progressing phenotype to a non-classical, slowly progressing phenotype Kantaputra et al, 2014;Zanetti et al, 2014). Of note, Leu321 is not conserved between the arylsulfatases, and the effect of the p.(Leu321Pro) mutation on the secondary structure of ASB is not known .…”

Section: Asb Structure and Variants Of Special Interestmentioning

confidence: 99%

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Mucopolysaccharidosis type VI (MPS VI) and molecular analysis: Review and classification of published variants in theARSBgene

et al. 2018

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Maroteaux–Lamy syndrome (MPS VI) is an autosomal recessive lysosomal storage disorder caused by pathogenic ARSB gene variants, commonly diagnosed through clinical findings and deficiency of the arylsulfatase B (ASB) enzyme. Detection of ARSB pathogenic variants can independently confirm diagnosis and render genetic counseling possible. In this review, we collect and summarize 908 alleles (201 distinct variants, including 3 polymorphisms previously considered as disease‐causing variants) from 478 individuals diagnosed with MPS VI, identified from literature and public databases. Each variant is further analyzed for clinical classification according to American College of Medical Genetics and Genomics (ACMG) guidelines. Results highlight the heterogeneity of ARSB alleles, with most unique variants (59.5%) identified as missense and 31.7% of unique alleles appearing once. Only 18% of distinct variants were previously recorded in public databases with supporting evidence and clinical significance. ACMG recommends publishing clinical and biochemical data that accurately characterize pathogenicity of new variants in association with reporting specific alleles. Variants analyzed were sent to ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/), and MPS VI locus‐specific database (http://mps6-database.org) where they will be available. High clinical suspicion coupled with diagnostic testing for deficient ASB activity and timely submission and classification of ARSB variants with biochemical and clinical data in public databases is essential for timely diagnosis of MPS VI.

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Section: Variantsmentioning

confidence: 85%

Section: Variantsmentioning

confidence: 99%

Section: Asb Structure and Variants Of Special Interestmentioning

confidence: 99%

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Mucopolysaccharidosis type VI (MPS VI) and molecular analysis: Review and classification of published variants in theARSBgene

et al. 2018

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“…However, even in the presence of a recurrent mutation, some patients carrying the same molecular lesion may present with different clinical phenotypes, suggesting that other variants at other gene loci and/or some environmental factors can modulate the clinical phenotype. This may be particularly important in the case of parents’ consanguinity, which is quite common in some ethnic groups due to geographical reasons or to the practice of arranged marriages [ 23 – 25 ].…”

Section: Introductionmentioning

confidence: 99%

Biochemical and molecular analysis in mucopolysaccharidoses: what a paediatrician must know

et al. 2018

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Mucopolysaccharidoses (MPS) are rare inherited disorders caused by a deficit of the lysosomal hydrolases involved in the degradation of mucopolysaccharides, also known as glycosaminoglycans (GAGs). They are all monogenic defects, transmitted in an autosomal recessive way, except for MPS type II which is X-linked. The enzymatic deficit causes a pathologic accumulation of undegraded or partially degraded substrates inside lysosomes as well as in the extracellular compartment. MPS generally present with recognizable signs and symptoms to raise a clinical suspicion. However, although they have individual peculiarities, often signs and symptoms may overlap between different MPS types. Therefore, a deeper evaluation of specific disease biomarkers becomes necessary to reach an appropriate diagnosis. This paper stresses the central role of the laboratory in completing and confirming the clinical suspicion of MPS according to a standardized procedure: first, a biochemical evaluation of the patient samples, including qualitative/quantitative urinary GAG analysis and a determination of enzyme activities, and then the molecular diagnosis. We also encourage a constant and close communication between clinicians and laboratory personnel to address a correct and early MPS diagnosis.

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“…Most mutations are “private”. Some mutations are common, and a few of them have been attributed to founder effect [1] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] ( [20] cited from Abstract). Study of influence of missense mutations on the overall structure and folding of ARSB helps to predict disease severity [24] , [25] .…”

Section: Introductionmentioning

confidence: 99%

Mutations in ARSB in MPS VI patients in India

Mathew

Jagadeesh

Bhat

et al. 2015

Molecular Genetics and Metabolism Reports

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Mucopolysaccharidosis VI (MPS VI) is an autosomal recessive inborn error of metabolism caused by mutations in the arylsulfatase B gene (ARSB) and consequent deficient activity of ARSB, a lysosomal enzyme. We present here the results of a study undertaken to identify the mutations in ARSB in MPS VI patients in India. Around 160 ARSB mutations, of which just 4 are from India, have been reported in the literature. Our study covered nine MPS VI patients from eight families. Both familial mutations were found in seven families, and only one mutation was found in one family. Seven mutations were found — four novel (p.G38_G40del3, p.C91R, p.L98R and p.R315P), two previously reported from India (p.D53N and p.W450C), and one reported from outside India (p.R160Q). One mutation, p.W450C, was present in two families, and the other six mutations were present in one family each. Analysis of the molecular structure of the enzyme revealed that most of these mutations either cause loss of an active site residue or destabilize the structure of the enzyme. The only previous study on mutations in ARSB in Indian MPS VI patients, by Kantaputra et al. 2014 [1], reported four novel mutations of which two (p.D53N and p.W450C) were found in our study as well. Till date, nine mutations have been reported from India, through our study and the Kantaputra study. Eight out of these nine mutations have been found only in India. This suggests that the population studied by us might have its own typical set of mutations, with other populations equally likely to have their own set of mutations.

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Molecular Analysis of Turkish Maroteaux-Lamy Patients and Identification of One Novel Mutation in the Arylsulfatase B (ARSB) Gene

Cited by 5 publications

References 27 publications

Mucopolysaccharidosis type VI (MPS VI) and molecular analysis: Review and classification of published variants in theARSBgene

Mucopolysaccharidosis type VI (MPS VI) and molecular analysis: Review and classification of published variants in theARSBgene

Biochemical and molecular analysis in mucopolysaccharidoses: what a paediatrician must know

Mutations in ARSB in MPS VI patients in India

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