Mucopolysaccharidosis VII: clinical, biochemical and molecular investigation of a Brazilian family

Schwartz, Ida Vanessa Döederlein; Silva, L. R.; Leistner, Sandra; Todeschini, Luis Alberto; Burin, Maira G.; Pina-Neto, João Monteiro de; Islam, Rafiqul; Shah, Gul N.; Sly, William S.; Giugliani, Roberto

doi:10.1034/j.1399-0004.2003.00119.x

Cited by 15 publications

(13 citation statements)

References 18 publications

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“…Approximately 40% of the known GUSB mutations occur at CpG sites within the gene. The most common mutation is L176F, which has been found in several populations: American (Caucasian), Brazilian, British, Chilean, French, Mexican, Polish, Spanish, and Turkish ([125–127], reviewed in [124]). Genotype/phenotype analysis indicated that the most severe phenotype was associated with truncating mutations and with mutations affecting either the hydrophobic core or the modification of packing.…”

Section: Mucopolysaccharidosis VII (Sly's Syndrome)mentioning

confidence: 99%

Glycosaminoglycan Storage Disorders: A Review

Coutinho¹,

Lacerda

Alves³

2012

Biochemistry Research International

132

118

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Impaired degradation of glycosaminoglycans (GAGs) with consequent intralysosomal accumulation of undegraded products causes a group of lysosomal storage disorders known as mucopolysaccharidoses (MPSs). Characteristically, MPSs are recognized by increased excretion in urine of partially degraded GAGs which ultimately result in progressive cell, tissue, and organ dysfunction. There are eleven different enzymes involved in the stepwise degradation of GAGs. Deficiencies in each of those enzymes result in seven different MPSs, all sharing a series of clinical features, though in variable degrees. Usually MPS are characterized by a chronic and progressive course, with different degrees of severity. Typical symptoms include organomegaly, dysostosis multiplex, and coarse facies. Central nervous system, hearing, vision, and cardiovascular function may also be affected. Here, we provide an overview of the molecular basis, enzymatic defects, clinical manifestations, and diagnosis of each MPS, focusing also on the available animal models and describing potential perspectives of therapy for each one.

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Section: Mucopolysaccharidosis VII (Sly's Syndrome)mentioning

confidence: 99%

Glycosaminoglycan Storage Disorders: A Review

Coutinho¹,

Lacerda

Alves³

2012

Biochemistry Research International

132

118

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“…Their functions can be inhibited by L-aspartic acid. Some studies [40,41] have shown that the protein is involved in disease of mucopolysaccharidosis. These results indicate that the molecular mechanism of mucopolysaccharidosisis associated with the biological processes of carbohydrate metabolism, glycosaminoglycan catabolism and metabolism, hyaluronan catabolism and metabolism and small molecule metabolism, and the protein can be considered as a drug target to treat the disease by blocking these biological processes with small molecule of bioactivity (i.e., drug).…”

Section: Large-scale Identification Of Potential Drug Target Proteinsmentioning

confidence: 99%

Large-scale identification of potential drug targets based on the topological features of human protein–protein interaction network

Zou

Zhong

Liu

et al. 2015

Analytica Chimica Acta

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“…Among the recurrent mutations, the most prevalent are: c.526C>T (p.L176F), c.1244C>T (p.P415L), c.1222C>T (p.P408S), c.1856C>T (p.A619 V), c.646C>T (p.R216W), c.1144C>T (p.R382C), and c.1429C>T (p.R477W), accounting for 20.4, 4.9, 4.9, 4.9, 3.9, 3.9, and 3.9%, respectively [Tomatsu et al, 1990, 1991; Fukuda et al, 1991; Vervoort et al, 1993; Wu et al, 1994; Islam et al, 1996, 1998; Vervoort et al, 1996, 1997; Schwartz et al, 2003]. The p.L176F mutation has been identified in diverse ethnic populations while the p.P415L mutation and p.P415L/P408S double mutation, and the p.A619 V mutation have been detected only in Mexican and Japanese populations, respectively.…”

Section: Mps VII Mutations and Their Biological Relevancementioning

confidence: 99%

“…The most prevalent c.526C>T transitional mutation (p.L176F), originally found in two Mennonite siblings, was identified in 21 alleles of 11 patients from American (Caucasian), Brazilian, British, Chilean, French, Mexican, Polish, Spanish, and Turkish origins [Wu et al, 1994; Vervoort et al, 1996; Schwartz et al, 2003] (Sly, unpublished results). A total of 10 of 11 patients were homozygous for the mutation.…”

Section: Mps VII Mutations and Their Biological Relevancementioning

confidence: 99%

Mutations and polymorphisms in GUSB gene in mucopolysaccharidosis VII (Sly Syndrome)

et al. 2009

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Mucopolysaccharidosis VII (MPS VII; Sly syndrome) is an autosomal recessive disorder caused by a deficiency of b-glucuronidase (GUS, EC 3.2.1.31; GUSB). GUS is required to degrade glycosaminoglycans (GAGs), including heparan sulfate (HS), dermatan sulfate (DS), and chondroitin-4,6-sulfate (CS). Accumulation of undegraded GAGs in lysosomes of affected tissues leads to mental retardation, short stature, hepatosplenomegaly, bone dysplasia, and hydrops fetalis. We summarize information on the 49 unique, disease-causing mutations determined so far in the GUS gene, including nine novel mutations (eight missense and one splice-site). This heterogeneity in GUS gene mutations contributes to the extensive clinical variability among patients with MPS VII. One pseudodeficiency allele, one polymorphism causing an amino acid change, and one silent variant in the coding region are also described. Among the 103 analyzed mutant alleles, missense mutations accounted for 78.6%; nonsense mutations, 12.6%; deletions, 5.8%; and splice-site mutations, 2.9%. Transitional mutations at CpG dinucleotides made up 40.8% of all the described mutations. The five most frequent mutations (accounting for 44/103 alleles) were exonic point mutations, p.L176F, p.R357X, p.P408S, p.P415L, and p.A619 V. Genotype/phenotype correlation was attempted by correlating the effects of certain missense mutations or enzyme activity and stability within phenotypes. These were in turn correlated with the location of the mutation in the tertiary structure of GUS. A total of seven murine, one feline, and one canine model of MPS VII have been characterized for phenotype and genotype.

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Mucopolysaccharidosis VII: clinical, biochemical and molecular investigation of a Brazilian family

Cited by 15 publications

References 18 publications

Glycosaminoglycan Storage Disorders: A Review

Glycosaminoglycan Storage Disorders: A Review

Large-scale identification of potential drug targets based on the topological features of human protein–protein interaction network

Mutations and polymorphisms in GUSB gene in mucopolysaccharidosis VII (Sly Syndrome)

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