NM_000308.4(CTSA):c.60del (p.Ser21fs) AND Combined deficiency of sialidase AND beta galactosidase

Clinical significance:Pathogenic (Last evaluated: Apr 16, 2021)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001420871.1

Allele description [Variation Report for NM_000308.4(CTSA):c.60del (p.Ser21fs)]

NM_000308.4(CTSA):c.60del (p.Ser21fs)

Gene:
CTSA:cathepsin A [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
20q13.12
Genomic location:
Preferred name:
NM_000308.4(CTSA):c.60del (p.Ser21fs)
HGVS:
  • NC_000020.11:g.45891628del
  • NG_008291.1:g.5677del
  • NG_033108.1:g.4660del
  • NM_000308.4:c.60delMANE SELECT
  • NM_001127695.2:c.60del
  • NM_001167594.2:c.114del
  • NP_000299.3:p.Ser21fs
  • NP_001121167.1:p.Ser21fs
  • NP_001161066.1:p.Ser39fs
  • NC_000020.10:g.44520267del
  • NM_000308.3:c.114delG
  • NR_133656.1:n.1296del
Protein change:
S21fs
Molecular consequence:
  • NM_000308.4:c.60del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001127695.2:c.60del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001167594.2:c.114del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NR_133656.1:n.1296del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Combined deficiency of sialidase AND beta galactosidase (GSL)
Synonyms:
CATHEPSIN A DEFICIENCY; Galactosialidosis; Goldberg syndrome; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009737; MedGen: C0268233; Orphanet: 351; OMIM: 256540

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001623291Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(Apr 16, 2021)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

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

Citations

PubMed

Galactosialidosis: historic aspects and overview of investigated and emerging treatment options.

Annunziata I, d'Azzo A.

Expert Opin Orphan Drugs. 2017;5(2):131-141. doi: 10.1080/21678707.2016.1266933. Epub 2016 Dec 14.

PubMed [citation]
PMID:
28603679
PMCID:
PMC5461780

Galactosialidosis: review and analysis of CTSA gene mutations.

Caciotti A, Catarzi S, Tonin R, Lugli L, Perez CR, Michelakakis H, Mavridou I, Donati MA, Guerrini R, d'Azzo A, Morrone A.

Orphanet J Rare Dis. 2013 Aug 2;8:114. doi: 10.1186/1750-1172-8-114. Review.

PubMed [citation]
PMID:
23915561
PMCID:
PMC3737020
See all PubMed Citations (5)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001623291.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

Variant summary: CTSA c.114delG (p.Ser39ProfsX71) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 8.3e-06 in 242104 control chromosomes. c.114delG has been reported in the literature in homozygous and compound heterozygous individuals affected with Galactosialidosis (e.g. Malvagia_2004, Caciotti_2013). These data indicate that the variant is likely to be associated with disease. Several publications report a reduction in beta-galactosidase (GLB1) and neuramidase (NEU1) enzymatic acitvity in fibroblasts from patients with the variant (e.g.Malvagia_2004, Caciotti_2013). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.

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

Last Updated: Jun 14, 2021

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