Missense mutations as a cause of metachromatic leukodystrophy

@article{Poeppel2005MissenseMA,
  title={Missense mutations as a cause of metachromatic leukodystrophy},
  author={Peter Poeppel and Matthias Habetha and Ana Marc{\~a}o and Heinrich Büssow and Linda Bern{\'a} and Volkmar Gieselmann},
  journal={The FEBS Journal},
  year={2005},
  volume={272}
}
Metachromatic leukodystrophy is a lysosomal storage disorder caused by a deficiency of arylsulfatase A (ASA). Biosynthesis studies of ASA with various structure‐sensitive monoclonal antibodies reveal that some epitopes of the enzyme form within the first minutes of biosynthesis whereas other epitopes form later, between 10 and 25 min. When we investigated 12 various ASAs, with amino acid substitutions according to the missense mutations found in metachromatic leukodystrophy patients… Expand
Metachromatic leukodystrophy: genetics, pathogenesis and therapeutic options
TLDR
Mice generated as a model of metachromatic leukodystrophy are used in various therapeutic trials involving enzyme replacement, haematopoietic stem‐cell‐based gene therapy and direct injections of ASA‐expressing viral vectors into the brain. Expand
Characterization of new arylsulfatase A gene mutations reinforces genotype‐phenotype correlation in metachromatic leukodystrophy
TLDR
Eight newly identified ARSA mutations are characterized, through lentiviral vector‐based expression studies on cell lines and ARSA defective murine fibroblasts, and the residual activity associated with the new mutant allele correlates well with the patient's phenotype. Expand
Metachromatic leukodystrophy – mutation analysis provides further evidence of genotype–phenotype correlation
TLDR
A correlation between ARSA gene mutations, age at onset and patterns of disease progression, was confirmed, not only in those patients bearing common mutations, but also in those carrying rare mutant alleles. Expand
Induction of Tolerance to Human Arylsulfatase A in a Mouse Model of Metachromatic Leukodystrophy
TLDR
Long-term, low-dose ERT reduced sulfatide storage in peripheral tissues and the central nervous system indicating that high levels of extracellular mutant hASA do not prevent cellular uptake and lysosomal targeting of substituted wildtype hASS. Expand
Identification of Novel ARSA Mutations in Chinese Patients with Metachromatic Leukodystrophy
TLDR
The present study discovered 28 novel ARSA mutations and widely expanded the mutation spectrum of ARSA, providing critical information for MLD families. Expand
An Italian Cohort Study Identifies Four New Pathologic Mutations in the ARSA Gene
TLDR
The data show once more that there are still several mutations to be discovered in the ARSA gene and there are rarely repeating ones found in the population, and the predictive value of the enzyme activity tests in regard to clinical manifestations is extremely limited. Expand
Developing therapeutic approaches for metachromatic leukodystrophy
TLDR
Current and future therapeutic strategies will be complementary, whether used in combination or separately at specific stages of the disease course, to produce better outcomes for patients afflicted with this devastating inherited disorder. Expand
Metachromatic leukodystrophy
TLDR
This review discusses pathogenesis, clinical manifestations, diagnostic process and efficacy of current and possible future therapies such as enzyme replacement therapy, hematopoietic stem cell transplantation and gene therapy for metachromatic leukodystrophy. Expand
Mutation Update of ARSA and PSAP Genes Causing Metachromatic Leukodystrophy
TLDR
An extensive review of all the ARSA‐ and PSAP‐causative variants published in the literature to date, accounting for a total of 200 ARSA and 10 PSAP allele types, is presented. Expand
Metachromatic Leukodystrophy: A Rare Case Report
A case of a rare disease known as Metachromatic leukodystrophy in a 7 year old male patient was reported to the Department of Pedodontics and Preventive Dentistry, Darshan Dental College andExpand
...
1
2
3
...

References

SHOWING 1-10 OF 32 REFERENCES
Molecular basis of late infantile metachromatic leukodystrophy in the Habbanite Jews
TLDR
Observations confirm the genealogical data which pointed to a common ancestor for all the carriers of MLD among the Habbanite Jews, and the same mutation was demonstrated to be relatively frequent among the Yemenite Jews. Expand
Characterization of two arylsulfatase A missense mutations D335V and T274M causing late infantile metachromatic leukodystrophy
TLDR
Examination of the effects of the mutation in cells stably overexpressing the mutant enzymes revealed, that the mutant enzyme is catalytically inactive and degraded in an early biosynthetic compartment. Expand
High residual arylsulfatase A (ARSA) activity in a patient with late-infantile metachromatic leukodystrophy.
TLDR
A patient suffering from late-infantile metachromatic leukodystrophy who has a residual arylsulfatase A (ARSA) activity of about 10%. Expand
The functional consequences of mis-sense mutations affecting an intra-molecular salt bridge in arylsulphatase A.
TLDR
The position of residue 370 in the three-dimensional structure of the enzyme provides a plausible explanation for the differing severities in loss of enzyme function caused by the mutations and thus the clinical phenotype. Expand
Juvenile and adult metachromatic leukodystrophy: partial restoration of arylsulfatase A (cerebroside sulfatase) activity by inhibitors of thiol proteinases.
TLDR
Inhibitors of thiol proteinases may be of therapeutic value in variants of metachromatic leukodystrophy, in which an unstable arylsulfatase A is synthesized. Expand
Characterization of four arylsulfatase A missense mutations G86D, Y201C, D255H, and E312D causing metachromatic leukodystrophy.
TLDR
Metachromatic leukodystrophy is a lysosomal storage disease caused by the deficiency of arylsulfatase A, and metabolic labeling experiments indicated that except for the E312D substitution the mutations cause arrest of the mutant arypsine A polypeptides in a prelysosomal compartment. Expand
A missense mutation P136L in the arylsulfatase A gene causes instability and loss of activity of the mutant enzyme
TLDR
Sequencing of the arylsulfatase A genes of an Ashkenazi Jewish patient suffering from the severe late infantile form of the disease revealed a point mutation in exon 2 causing proline 136 to be substituted by leucine. Expand
Biochemical characterization of two (C300F, P425T) arylsulfatase a missense mutations
TLDR
The characterization of the biochemical effects of two arylsulfatase A missense mutations, P425T and C300F, shows that the mutant proteins can pass the Golgi apparatus and thus are not degraded in the endoplasmic reticulum, but in the lysosomes. Expand
Late‐onset metachromatic leukodystrophy: Molecular pathology in two siblings
TLDR
A comparison of genotypes, ARSA activities, and clinical data on 4 individuals carrying the allele of 81 patients with MLD examined, further validates the concept that different degrees of residual ARSA activity are the basis of phenotypical variation in MLD. Expand
Accelerated transport and maturation of lysosomal α–galactosidase A in Fabry lymphoblasts by an enzyme inhibitor
TLDR
1–deoxy–galactonojirimycin (DGJ), a potent competitive inhibitor of α–Gal A, effectively enhanced α-Gal A activity in Fabry lymphoblasts, when administrated at concentrations lower than that usually required for intracellular inhibition of the enzyme. Expand
...
1
2
3
4
...