Four novel mutant alleles of the arylsulfatase B gene in two patients with intermediate form of mucopolysaccharidosis VI (Maroteaux-Lamy syndrome)

Abstract

Mucopolysaccharidosis type VI (MPSVI, Maroteaux-Lamy syndrome) is a lysosomal storage disease for which multiple clinical phenotypes have been described. A deficiency of the enzyme arylsulfatase B (ASB, N-acetylgalactosamine-4-sulfatase) is the cause of this autosomal recessively inherited disorder. The genotypes of two patients with an intermediate form of MPSVI have been determined by polymerase chain reaction (PCR) amplification of the entire open reading frame of the ASB gene and subsequent direct sequencing of both strands of the PCR fragments by an automated nonradioactive approach. In patient A, a C to T transition in allele I resulting in an exchange of the Arg codon 160 for a premature stop codon (R160*, exon 2), and a G to A transition in allele II leading to a Gln to Arg160 substitution (R160Q, exon 2) were detected. Patient B exhibited a 7-bp deletion in exon 1 of allele I resulting in a frame shift and a premature stop codon 33 triplets 3' of the site of deletion (delta G237-C243), and a C to T transition in allele II giving rise to a Trp to Arg152 substitution (R152W, exon 2). None of these four mutant alleles was present among 60 alleles of the ASB gene in unrelated controls, indicating that the former are not polymorphisms. These results emphasize the broad molecular heterogeneity of Maroteaux-Lamy syndrome and contribute to the establishment of a genotype/phenotype correlation in this disease.

Mutational analysis of mucopolysaccharidosis type VI patients undergoing a trial of enzyme replacement therapy

“…With the cloning of the ARSB gene [Peters et al, 1990;Schuchman et al, 1990;Litjens et al, 1991] and advances in sequencing technology, the identification and analysis of ARSB mutations was made possible [Wicker et al, 1991;Jin et al, 1992;Litjens et al, 1992;Arlt et al, 1994;Isbrandt et al, 1994;Voskoboeva et al, 1994;Litjens et al, 1996;Villani et al, 1999;Litjens and Hopwood, 2001]. In recent times, advances in mass spectrometry technology have led to more accurate determination of storage material (Ramsay et al, 2003).…”

Identification of a Novel Mutation in the ARSB Gene That Is Frequent Among Brazilian MPSVI Patients

“…Thus, the severe, or infantile, form is usually diagnosed before 2 years of age. In the mild, or adult, form the diagnosis is made after 20 years of age, and in the intermediate, or juvenile, form, the diagnosis is established between 2 and 20 years of age (Voskoboeva et al, 1994).…”

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

“…Until now, analyses of ARSB gene mutations have been reported for many world populations including the North Jin et al 1992;Karageorgos et al 2007a;Simonaro and Schuchman 1995) and the South American (Karageorgos et al 2007a;Petry et al 2003Petry et al , 2005, the Western European Isbrandt et al 1994Isbrandt et al , 1996Karageorgos et al 2007a;Villani et al 1998Villani et al , 1999, the Eastern European Jurecka et al 2012;Voskoboeva et al 1994Voskoboeva et al , 2000, the Asiatic (Dou et al 2006;Wicker et al 1991;Wu et al 2000), and the Australian populations (Litjens et al 1992(Litjens et al , 1996Wicker et al 1991). Three studies have been published describing few cases of mucopolysaccharidoses in the Turkish population (Elcioglu et al 2009;Emre et al 2000;Terzioglu et al 2002).…”