NM_000512.4(GALNS):c.421T>A (p.Trp141Arg) AND Morquio syndrome

Clinical significance:Likely pathogenic (Last evaluated: Jun 14, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000282371.1

Allele description

NM_000512.4(GALNS):c.421T>A (p.Trp141Arg)

Gene:
GALNS:galactosamine (N-acetyl)-6-sulfatase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16q24.3
Genomic location:
Preferred name:
NM_000512.4(GALNS):c.421T>A (p.Trp141Arg)
HGVS:
  • NC_000016.10:g.88840993A>T
  • NG_008667.1:g.20974T>A
  • NM_000512.4:c.421T>A
  • NM_001323543.1:c.-135T>A
  • NP_000503.1:p.Trp141Arg
  • NC_000016.9:g.88907401A>T
  • P34059:p.Trp141Arg
Protein change:
W141R
Links:
UniProtKB: P34059#VAR_007190; dbSNP: rs794727625
NCBI 1000 Genomes Browser:
rs794727625
Molecular consequence:
  • NM_001323543.1:c.-135T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000512.4:c.421T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Morquio syndrome
Synonyms:
Mucopolysaccharidosis, Type IV; MPS IV; Mucopolysaccharidosis type 4
Identifiers:
MedGen: C0026707; Orphanet: 582

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000399654Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Likely pathogenic
(Jun 14, 2016)
germlineclinical testing

PubMed (8)
[See all records that cite these PMIDs]

ICSL_Variant_Classification_20161018.pdf

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Identification of 31 novel mutations in the N-acetylgalactosamine-6-sulfatase gene reveals excessive allelic heterogeneity among patients with Morquio A syndrome.

Bunge S, Kleijer WJ, Tylki-Szymanska A, Steglich C, Beck M, Tomatsu S, Fukuda S, Poorthuis BJ, Czartoryska B, Orii T, Gal A.

Hum Mutat. 1997;10(3):223-32.

PubMed [citation]
PMID:
9298823
See all PubMed Citations (8)

Details of each submission

From Illumina Clinical Services Laboratory,Illumina, SCV000399654.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

The c.421T>A (p.Trp141Arg) variant has been reported in two studies in which it was identified in a homozygous state in two patients with mucopolysaccharidosis type IV, both exhibiting a severe phenotype (Bunge et al. 1997; Khedhiri et al. 2014). The p.Trp141Arg variant was absent from the 116 evaluated control chromosomes and is not observed in the 1000 Genomes Project, the Exome Sequencing Project, or the Exome Aggregation Consortium in spite of good coverage, suggesting it is rare. Negligible GALNS activity was observed in leukocytes extracted from one of these patients (Khedhiri et al. 2014). Trp141 is a well-conserved residue. Structural studies of the 3D structure of human GALNS demonstrated that the residue is located in the hydrophobic core of the enzyme near the active site (Rivera-Colon et al. 2012). Based on the available evidence, the p.Trp141Arg variant is classified as likely pathogenic for mucopolysaccharidosis type IV.

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

Last Updated: Apr 2, 2018