Mucopolysaccharidosis type VI: Identification of novel mutations on the arylsulphatase B gene in South American patients

Abstract

Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome, MPS VI) is an autosomal recessive disorder caused by deficiency of N-acetylgalactosamine-4-sulphatase (ARSB),which leads to the lysosomal accumulation and excretion of dermatan sulphate (DS). In this study, 13 unrelated MPS VI patients (12 Brazilian and 1 Chilean) were investigated regarding the identification of the ARSB gene mutations using PCR, SSCP and sequencing. The exons with altered mobility on SSCP were sequenced, as well as all the exons of patients with no SSCP alteration. Seven novel mutations were identified: D59N, L72R, Q88H, P93S, R197X, 1279delA and c.1143-8T > G. The previously reported mutations 1533del23, R315Q and 427delG were found in six, three and two alleles respectively. The other mutations already reported, S384N and G144R, were found in only one allele. In addition, three polymorphisms previously described (V358M, V376M and P397P) were detected in the patients analysed. Our findings are in agreement with the literature confirming the great genetic heterogeneity associated with MPS VI.

A Community-Based Study of Mucopolysaccharidosis Type VI in Brazil: The Influence of Founder Effect, Endogamy and Consanguinity

“…The 4 deceased Monte Santo patients, 2 males and 2 females, were between 7 and 19 years of age at their death and, prior to death, they had also been shown to be homozygous for the p.H178L mutation ( table 1 ). By comparison, c.1533del23 has been reported to be the most common MPS VI mutation elsewhere in Brazil [22,23] . In addition to the 13 genomically confirmed cases, family members identified another 33 deceased persons with the characteristic MPS VI phenotype who had died at between 1 and 24 years of age ( table 2 ; fig.…”

“…The reactions were subjected to 5 min of initial denaturation at 94 ° C, and 30 cycles of denaturation at 94 ° C for 40 s, annealing at 47 ° C for 40 s, and elongation at 72 ° C for 40 s, with a final extension step at 72 ° C for 10 min. The primers used to amplify the exon were the same as described by Petry et al [22] , and the PCR products were analyzed in 1.5% agarose gels containing ethidium bromide.…”

Short Communication Impact of early enzyme-replacement therapy for mucopolysaccharidosis VI: results of a long-term follow-up of Brazilian siblings

“…A biochemical diagnosis led to the detection of MPS VI when she was 3 years old. Molecular analysis of the ARSB gene identified the homozygous mutation c.1143-8T>G, which has been previously characterized in MPS VI patients (Petry et al, 2005;Garrido et al, 2008). At that time, she has already developed mitral and aortic lesions, along with a dilated and hypertrophic left ventricle.…”

Attenuated osteoarticular phenotype of type VI mucopolysaccharidosis: a report of four patients and a review of the literature

“…Apart from severe and attenuated phenotypes, descriptive classification systems have also described an intermediate disease form. Other authors suggested other classification systems based on height and urinary glycosaminoglycan (uGAG) levels, the age at the onset of symptoms, patient’s height, and the age of death [16, 17]. In reality, there are no fixed parameters to ascribe a particular patient to a single category, and the decision is subjective depending on physician’s experience and knowledge.…”