CLCN5, ALU INS, EX11 AND Dent disease 1

Clinical significance:Pathogenic (Last evaluated: Dec 7, 2010)

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:
RCV000012575.23

Allele description [Variation Report for CLCN5, ALU INS, EX11]

CLCN5, ALU INS, EX11

Gene:
CLCN5:chloride channel, voltage-sensitive 5 [Gene - OMIM]
Variant type:
Insertion
Cytogenetic location:
Xp11.22
Preferred name:
CLCN5, ALU INS, EX11
HGVS:
    Nucleotide change:
    ALU INS, EX11
    Links:
    OMIM: 300008.0012

    Condition(s)

    Name:
    Dent disease 1 (NPHL2)
    Synonyms:
    NEPHROLITHIASIS, HYPERCALCIURIC, X-LINKED; Nephrolithiasis, hypercalciuria X-linked; Urolithiasis, hypercalciuric X-linked; See all synonyms [MedGen]
    Identifiers:
    MedGen: C1848336; Orphanet: 1652; Orphanet: 93622; OMIM: 300009
    Age of onset:
    Childhood

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    Assertion and evidence details

    Submission AccessionSubmitterReview Status
    (Assertion method)
    Clinical Significance
    (Last evaluated)
    OriginMethodCitations
    SCV000032809OMIMno assertion criteria providedPathogenic
    (Dec 7, 2010)
    germlineliterature only

    PubMed (2)
    [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

    The Alu insertion in the CLCN5 gene of a patient with Dent's disease leads to exon 11 skipping.

    Claverie-Martín F, Flores C, Antón-Gamero M, González-Acosta H, García-Nieto V.

    J Hum Genet. 2005;50(7):370-4. Epub 2005 Jul 23.

    PubMed [citation]
    PMID:
    16041495

    De novo insertion of an Alu sequence in the coding region of the CLCN5 gene results in Dent's disease.

    Claverie-Martin F, González-Acosta H, Flores C, Antón-Gamero M, García-Nieto V.

    Hum Genet. 2003 Nov;113(6):480-5. Epub 2003 Aug 29.

    PubMed [citation]
    PMID:
    14569459

    Details of each submission

    From OMIM, SCV000032809.1

    #EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
    1not providednot providednot providednot providedliterature only PubMed (2)

    Description

    Claverie-Martin et al. (2003) studied a Spanish patient with Dent disease (300009) and found, by PCR amplification of the CLCN5 exons, an abnormally large exon 11. Sequence analysis showed an insertion in codon 650 of a 345-bp Alu element that had arisen de novo on the maternal chromosome. Polymorphism analysis indicated that the insertion occurred in the germline of the maternal grandfather. The presence of a long poly(A) tract and evidence for a 16-bp target-site duplication implied that the Alu element was integrated by retrotransposition. The mutation predicted a truncated CLC5 protein.

    Claverie-Martin et al. (2005) reported further studies of the Alu insertion in the family previously reported by Claverie-Martin et al. (2003). PCR amplification of blood DNA showed that the Alu insertion resulted in aberrant splicing of the CLCN5 pre-mRNA and skipping of exon 11. The resultant truncated protein lacks part of the C terminus, including the PY and CBS2 domains, which are critical for sorting and chloride channel function. In addition, there were 2 conserved exonic splicing enhancer sequences in the site of insertion.

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

    Last Updated: Jun 19, 2015