Pseudodeficiency of arylsulfatase A: a common genetic polymorphism with possible disease implications

@article{Hohenschutz2004PseudodeficiencyOA,
  title={Pseudodeficiency of arylsulfatase A: a common genetic polymorphism with possible disease implications},
  author={Charlotte Hohenschutz and P Eich and Waltraut Friedl and Abdul Waheed and Ernst Conzelmann and P. Propping},
  journal={Human Genetics},
  year={2004},
  volume={82},
  pages={45-48}
}
SummaryAt the locus for arylsulfatase A (ASA) at least four to five alleles exist: besides the normal ASA+ and at least two to three deficiency alleles (ASA-), a pseudodeficiency allele, ASAp, is known. On SDS-PAGE the ASAp enzyme migrates slightly faster than ASA+. Treatment of extracts from cells with ASA+/ASA+, ASAp/ASAp, or ASA+/ASAp genotypes with endoglycosidase F leads to the same deglycosylated subunit pattern. Presumably the degree of glycosylation is lower in ASAp than in ASA+. In a… Expand
Genotype-phenotype relationship in various degrees of arylsulfatase A deficiency
TLDR
This work has studied the relationship between the ASA genotype and the clinical phenotype, and defined three different classes of ASA deficiency: homozygosity for the pseudodeficiency allele (ASAP), compound heterozygosityfor the ASAP and MLD (ASA−) alleles, and ASA−/ ASA− genotypes. Expand
Pseudodeficiency of arylsulphatase A: Strategy for clarification of genotype in families of subjects with low ASA activity and neurological symptoms
TLDR
A strategy for cases with low ASA activity and neurological symptoms in families carrying a PD allele or both PD and MLD alleles is proposed and an allele containing the PD2 mutation alone is proposed. Expand
Population frequency of the arylsulphatase A pseudo-deficiency allele
TLDR
An A to G nucleotide transition in the first polyadenylation signal of the ASA gene results in the loss of its major mRNA species and a greatly reduced level of enzyme activity, which is the cause of ASA pseudo-deficiency. Expand
Disease-causing mutations in cis with the common arylsulfatase A pseudodeficiency allele compound the difficulties in accurately identifying patients and carriers of metachromatic leukodystrophy.
TLDR
It is estimated that 1-2% of Pd alleles will have a disease-causing mutation, and this complicates the identification of patients and the assignment of risk for a couple when a copy of the Pd allele is detected. Expand
An assay for the rapid detection of the arylsulfatase A pseudodeficiency allele facilitates diagnosis and genetic counseling for metachromatic leukodystrophy
TLDR
A non-radioactive assay based on the polymerase chain reaction is described, which allows the rapid detection of the ASA pd allele and utilizes pairs of primers that allow either the amplification ofThe ASA PD allele or of other ASA alleles. Expand
Prevalence of common mutations in the arylsulphatase A gene in metachromatic leukodystrophy patients diagnosed in Britain
The frequency of two common disease-associated mutations in the arylsulphatase A (ASA) gene, and of a mutation causing ASA pseudodeficiency, have been established in metachromatic leukodystrophyExpand
Arylsulfatase A pseudodeficiency in Chinese
TLDR
The data suggest that the A2725G mutation occurred in DNA that already contained the A1788G change, at an ancient time in one of the authors' common ancestors. Expand
Croatian population data for arylsulfatase a pseudodeficiency-associated mutations in healthy subjects, and in patients with Alzheimer-type dementia and Down syndrome.
TLDR
Frequency of two mutations associated with ASA pseudodeficiency in the Croatian population is slightly below the range reported for other populations, and despite the proposed role of arylsulfatase A pseudodficiency as one of the predisposing factors for neuropsychiatric disorders, the preliminary results did not show significantly higher frequencies. Expand
Advances in the molecular genetics of metachromatic leukodystrophy
TLDR
The gene for arylsulphatase A has recently been cloned and provides a necessary tool for the exact description of the molecular defects occurring in the different forms of metachromatic leukodystrophy. Expand
Molecular genetics of metachromatic leukodystrophy
TLDR
The characterization of the mutations causing pseudodeficiency has allowed the detection of the pseudodficiency allele in the DNA of probands and has thus improved the diagnosis and genetic counselling for metachromatic leukodystrophy. Expand
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TLDR
The results imply that the ASA that is formed in this condition has properties similar to those of the normal hydrolase, so that even if it is synthesized in lower amounts, it is still sufficient to promote normal catabolism of sulfatide. Expand
Probable metachromatic leukodystrophy/pseudodeficiency compound heterozygote at the arylsulfatase A locus with neurological and psychiatric symptomatology.
TLDR
A female patient, who had been first hospitalized with the diagnosis encephalomyelitis disseminata, is presented and it appears probable that in this patient low ASA activity leads to the accumulation of sulfatide and either causes the appearance of neuropsychiatric symptoms or at least contributes to the demyelination process. Expand
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TLDR
A genetic analysis was performed in an isolate in which metachromatic leukodystrophy (MLD) and aryl sulfatase A (ASA) pseudodeficiency are relatively frequent, and two independent pedigrees including MLD patients and ASA-deficient healthy individuals also fit the model of allelism. Expand
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TLDR
Analysis of residual arylsulfatase A activity with either Cellogel electrophoresis or isoelectric focusing in polyacrylamide gels now has been shown to distinguish between them unequivocally and can be adapted easily for general laboratory analysis in cases when results from quantitative ariesulfatases A assays are noninformative. Expand
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TLDR
The two allelic forms of the arylsulfatase A polypeptides were converted into a 57-kDa form by endo-beta-N-acetylglucosaminidase H, an enzyme specifically removing asparagine-linked oligosaccharides of the high-mannose (and hybrid) type. Expand
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TLDR
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TLDR
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TLDR
It is reported that with metabolic labelling, cultured pseudo deficient cells synthesized about 20% of the normal amount of arylsulfatase A at a reduced rate of apparent synthesis and increased rate of degradation, but in the presence of ammonium chloride which stimulated secretion of lysosomal enzymes, this defect is associated with labile ariesulfatases A molecules which can be stabilized if they are diverted from intracellular storage. Expand
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TLDR
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