NM_000487.6(ARSA):c.1279C>A (p.Pro427Thr) AND Metachromatic leukodystrophy, juvenile type

Clinical significance:Pathogenic (Last evaluated: Jun 20, 2003)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000003240.3

Allele description [Variation Report for NM_000487.6(ARSA):c.1279C>A (p.Pro427Thr)]

NM_000487.6(ARSA):c.1279C>A (p.Pro427Thr)

Gene:
ARSA:arylsulfatase A [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
22q13.33
Genomic location:
Preferred name:
NM_000487.6(ARSA):c.1279C>A (p.Pro427Thr)
Other names:
P425T
HGVS:
  • NC_000022.11:g.50625396G>T
  • NG_009260.2:g.7784C>A
  • NM_000487.6:c.1279C>AMANE SELECT
  • NM_001085425.3:c.1279C>A
  • NM_001085426.3:c.1279C>A
  • NM_001085427.3:c.1279C>A
  • NM_001085428.3:c.1021C>A
  • NM_001362782.2:c.1021C>A
  • NP_000478.3:p.Pro427Thr
  • NP_001078894.2:p.Pro427Thr
  • NP_001078895.2:p.Pro427Thr
  • NP_001078896.2:p.Pro427Thr
  • NP_001078897.1:p.Pro341Thr
  • NP_001349711.1:p.Pro341Thr
  • NC_000022.10:g.51063824G>T
Protein change:
P341T; PRO425THR
Links:
OMIM: 607574.0047; dbSNP: rs74315485
NCBI 1000 Genomes Browser:
rs74315485
Molecular consequence:
  • NM_000487.6:c.1279C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001085425.3:c.1279C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001085426.3:c.1279C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001085427.3:c.1279C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001085428.3:c.1021C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001362782.2:c.1021C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Metachromatic leukodystrophy, juvenile type
Synonyms:
Metachromatic leukodystrophy, juvenile form
Identifiers:
MONDO: MONDO:0009591; MedGen: C0751276

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000023398OMIMno assertion criteria providedPathogenic
(Jun 20, 2003)
germlineliterature only

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Metachromatic leucodystrophy in Portugal-finding of four new molecular lesions: C300F, P425T, g.1190-1191insC, and g.2408delC. Mutations in brief no. 232. Online.

Marcão A, Amaral O, Pinto E, Pinto R, Sá Miranda MC.

Hum Mutat. 1999;13(4):337-8.

PubMed [citation]
PMID:
10220151

Biochemical characterization of two (C300F, P425T) arylsulfatase a missense mutations.

Marcão A, Simonis H, Schestag F, Sá Miranda MC, Gieselmann V.

Am J Med Genet A. 2003 Jan 30;116A(3):238-42.

PubMed [citation]
PMID:
12503099
See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000023398.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (3)

Description

In a patient with juvenile MLD (250100), Marcao et al. (1999, 2003) identified compound heterozygosity for a P426L (607574.0004) and a pro425-to-thr (P425T) mutation in the ARSA gene. Transfection experiments with P425T cDNA demonstrated residual ARSA enzyme activity of about 10% of normal, and resulted in more rapid enzyme degradation in lysosomes. Using sedimentation analysis of the mutated protein, Marcao et al. (2003) showed that the P425L mutation resulted in a modest reduction of the octamerization capacity of ARSA at low pH, which may be related to the reduced lysosomal half-life of the enzyme.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 7, 2021

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