Molecular analysis of the α-N-acetylglucosaminidase gene in seven Japanese patients from six unrelated families with mucopolysaccharidosis IIIB (Sanfilippo type B), including two novel mutations

Tanaka, Akemi; Kimura, Michio; Lan, Hoàng Thị; Takaura, Natsuko; Yamano, Tunekazu

doi:10.1007/s100380200070

Cited by 15 publications

(14 citation statements)

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“…org), is responsible for cleaving the glycosidic bond found in the backbone of heparan and thus plays a key role in heparan recycling. More than 100 different mutations in the naglu gene have been associated with the MPS IIIB phenotype, and biochemical studies have confirmed the deleterious effects of many of these mutations (1)(2)(3)(4)(5)(6)(7)(8)(9). Despite having been cloned Ͼ10 years ago, no structural or mechanistic data for NAGLU have been obtained, hindering the development of potential therapeutic strategies to treat patients suffering from MPS IIIB.…”

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confidence: 99%

Structural and mechanistic insight into the basis of mucopolysaccharidosis IIIB

Ficko-Blean

Stubbs²,

Nemirovsky³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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confidence: 99%

Structural and mechanistic insight into the basis of mucopolysaccharidosis IIIB

Ficko-Blean

Stubbs²,

Nemirovsky³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…One polymorphism was found in the noncoding region, including g2739G fi C (intron 2; 10/10 alleles). Other polymorphisms, such as g1352insC, a2259A fi C, and g2304insA (Tanaka et al 2002), were not analyzed. To confirm the homozygous R565P mutation, SacII digestion of PCR products was performed using the engineered primers from five patients and both of the parents of P5.…”

Section: Resultsmentioning

confidence: 99%

“…Since little is known about the catalytic site and tertiary structure of the enzyme, it is very difficult to draw any conclusions on the effect of the missense mutation on enzyme function. However, two other missense mutations at Arg-565 (R565W and R565Q) have been reported in MPS IIIB patients with a severe phenotype (Beesley et al 1998;Bunge et al 1999;Weber et al 1999;Tanaka et al 2002). Arginine is positively charged and more hydrophilic than proline, which is uncharged and moderately polar (Nelson and Cox 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Since the Arg-565 codon (CGG) includes CpG dinucleotides, which are known to be relatively unstable for mutations (Vogel and Motulsky 1997), there may be many other missense mutations in Arg-565 in patients with MPS IIIB. Tanaka et al (2002) reported three MPS IIIB patients in two unrelated families from the Okinawa islands. Two siblings with an attenuated phenotype were compound heterozygous for R565P/F314L, and one patient with a severe phenotype was homozygous for R565P.…”

Section: Discussionmentioning

confidence: 99%

“…U43572) is located on chromosome 17q21.1 and contains six exons coding for 743 amino acids (Weber et al 1996;Zhao et al 1996). Tanaka et al (2002) reported three MPS IIIB patients in two families from the Okinawa islands with an R565P mutation. We analyzed the NAGLU gene in five patients with severe clinical profiles, excluding the above three patients.…”

Section: Introductionmentioning

confidence: 99%

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Sanfilippo type B syndrome: five patients with an R565P homozygous mutation in the α-N-acetylglucosaminidase gene from the Okinawa islands in Japan

et al. 2005

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Sanfilippo type B syndrome (mucopolysaccharidosis type IIIB; MPS IIIB) is an autosomal recessive lysosomal storage disorder that is caused by defective a-N-acetylglucosaminidase (NAGLU). We performed NAGLU gene analysis in five patients with MPS IIIB whose respective parents from the Okinawa islands in Japan were not apparently consanguineous. We found a missense mutation (R565P) in all five patients (all homozygotes). We screened this mutation in 200 healthy subjects and found one heterozygote (none of the subjects were related to the patients). These results suggest that there may be a founder effect that results in the accumulation of R565P mutation in this area.

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Clinical and Neuroradiological Aspects of the Different Types

Müller‐Forell

Frenking²,

Amraoui³

et al. 2007

Clin Neuroradiol

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The different types (I-VII) of mucopolysaccharidoses (MPS), a hereditary lysosomal storage disorder where the enzyme defect leads to glycosaminoglycan deposits in different tissues, present with characteristic lesions of the central nervous system (CNS). This review reports the CT and MRI findings of patients suffering from mucopolysaccharidosis in the context with aspects of biochemistry, pathophysiology, histological findings and clinical course. Neuroradiological findings include hydrocephalus, focal or global brain atrophy, and spinal cord compression at the atlantoaxial joint. Cribriform white matter lesions, corresponding to mucopolysaccharide deposition in the enlarged perivascular space, combined with leukencephalopathy are found in about half of the patients. Another half of the patients show minor to severe myelopathy at the atlantoaxial joint due to cervical cord compression. These findings are observed mainly in patients with MPS type IV, but as well in nearly all patients with MPS type VI. In the literature brain involvement is described exclusively in MPS type I, II and III, but the authors show definite demyelination and widening of the perivascular space in a number of patients with MPS type VI, who additionally suffered from progressive visual deficits, caused by ocular and/or optic nerve involvement. ZusammenfassungDie verschiedenen Formen der Mukopolysaccharidosen (MPS), einer hereditären, lysosomalen Speicherkrankheit, die, bedingt durch einen Enzymdefekt, zu Glykosaminoglykanablagerungen in verschiedenen Geweben führt, weisen charakteristische Veränderungen des zentralen Nervensystems (ZNS) aus. In dieser Übersichtsarbeit werden die CT-und MRT-Befunde von Patienten mit Mukopolysaccharidosen in Zusammenhang mit biochemischen, pathophysiologischen und pathohistologischen Befunden sowie charakteristischen klinischen Symptomen und im Verlauf vorgestellt. Die neuroradiologischen Befunde des ZNS weisen neben einem Hydrozephalus, einer fokalen und/oder globalen Atrophie auch eine medulläre Kompression am kraniozervikalen Übergang auf. Hinzu kommen erweiterte perivaskuläre Räume und Veränderungen der weißen Substanz. In jeweils etwa der Hälfte aller Patienten werden diese sog. cribriformen Läsionen (bedingt durch perivaskuläre Mukopolysaccharidablagerungen) und eine Leukenzephalopathie sowie eine hohe zervikale Myelonkompression mit unterschiedlich ausgeprägter Myelomalazie gefunden. Diese Befunde sind in erster Linie bei Patienten mit MPS IV, aber auch in der Mehrzahl der Patienten mit MPS VI zu finden. In der Literatur wird angegeben, dass eine ZNS-Beteiligung lediglich bei Patienten mit MPS I, II und III zu finden ist, die Autoren haben jedoch Demyelinisierung und erweiterte perivaskuläre Räume auch bei Patienten mit MPS VI nachgewiesen, die zusätzlich auch an progredienter Visusminderung litten, bedingt durch eine Beteiligung der Kornea und/oder des Nervus opticus. Schlüsselwörter: Mukopolysaccharidosen (MPS) · MR · Perivaskulärer Raum · Myelopathie · Leukenzephalopathie

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Molecular analysis of the α-N-acetylglucosaminidase gene in seven Japanese patients from six unrelated families with mucopolysaccharidosis IIIB (Sanfilippo type B), including two novel mutations

Cited by 15 publications

References 4 publications

Structural and mechanistic insight into the basis of mucopolysaccharidosis IIIB

Structural and mechanistic insight into the basis of mucopolysaccharidosis IIIB

Sanfilippo type B syndrome: five patients with an R565P homozygous mutation in the α-N-acetylglucosaminidase gene from the Okinawa islands in Japan

Clinical and Neuroradiological Aspects of the Different Types

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