NM_000391.4(TPP1):c.887-10A>G AND Ceroid lipofuscinosis neuronal 2

Clinical significance:Pathogenic (Last evaluated: Jan 1, 2008)

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:
RCV000002768.3

Allele description [Variation Report for NM_000391.4(TPP1):c.887-10A>G]

NM_000391.4(TPP1):c.887-10A>G

Gene:
TPP1:tripeptidyl peptidase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11p15.4
Genomic location:
Preferred name:
NM_000391.4(TPP1):c.887-10A>G
HGVS:
  • NC_000011.10:g.6616513T>C
  • NG_008653.1:g.7949A>G
  • NM_000391.4:c.887-10A>GMANE SELECT
  • LRG_830t1:c.887-10A>G
  • LRG_830:g.7949A>G
  • NC_000011.9:g.6637744T>C
  • NM_000391.3:c.887-10A>G
Note:
NCBI staff reviewed the sequence information reported in PubMed 17959406 Fig. 2 to determine the location of this allele on the current reference sequence.
Nucleotide change:
IVS7AS, A-G, -10
Links:
OMIM: 607998.0009; dbSNP: rs755445790
NCBI 1000 Genomes Browser:
rs755445790
Molecular consequence:
  • NM_000391.4:c.887-10A>G - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:
Ceroid lipofuscinosis neuronal 2 (CLN2)
Synonyms:
TPP1-Related Neuronal Ceroid-Lipofuscinosis
Identifiers:
MONDO: MONDO:0008769; MedGen: C1876161; Orphanet: 168491; Orphanet: 228349; Orphanet: 79264; OMIM: 204500

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000022926OMIMno assertion criteria providedPathogenic
(Jan 1, 2008)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

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

Citations

PubMed

CLN2/TPP1 deficiency: the novel mutation IVS7-10A>G causes intron retention and is associated with a mild disease phenotype.

Bessa C, Teixeira CA, Dias A, Alves M, Rocha S, Lacerda L, Loureiro L, GuimarĂ£es A, Ribeiro MG.

Mol Genet Metab. 2008 Jan;93(1):66-73. Epub 2007 Oct 23.

PubMed [citation]
PMID:
17959406

Details of each submission

From OMIM, SCV000022926.2

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

Description

In a 40-year-old Portuguese man with a mild protracted form of neuronal ceroid lipofuscinosis-2 (CLN2; 204500), Bessa et al. (2008) identified a homozygous A-to-G transition in intron 7 (IVS7AS-10A-G) of the TPP1 gene, which created a potential acceptor site predicted to result in 3 extra amino acids between codons 295 and 296 and not affecting the wildtype splice site. At age 10 years, the patient had onset of progressive cognitive and motor dysfunction and seizures. Leukocytes and fibroblasts showed decreased TPP1 activity compared to controls, but activity was about 2-fold higher than that associated with TPP1-null mutations. Northern blot analysis found normal levels of correctly spliced CLN2 mRNA in patient fibroblasts, but cDNA sequencing showed the retention of 9 nucleotides from intron 7, showing that the alternative splice site was used. Western blot analysis detected a 60% reduction in overall TPP1 protein levels, suggesting that the mutant protein had decreased stability. Each unaffected parent was heterozygous for the mutation, which was not found in 100 control chromosomes. Bessa et al. (2008) concluded that the mutant protein retained enzyme activity, which was consistent with the milder phenotype.

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

Last Updated: Nov 27, 2021

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