Germline mosaicism is a pitfall in the diagnosis of “sporadic” X-linked Alport syndrome View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-02

AUTHORS

Takayuki Okamoto, Kandai Nozu, Kazumoto Iijima, Tadashi Ariga

ABSTRACT

Approximately 80% of patients with Alport syndrome have X-linked Alport syndrome (XLAS), which is caused by mutations in the type IV collagen alpha 5 gene (COL4A5). In patients with XLAS, approximately 10-15% of COL4A5 mutations occur as spontaneous events. Here, we describe maternal germline mosaicism in a family of XLAS patients. Since our patient's parents showed normal urinary findings without COL4A5 mutation using genomic DNA isolated from peripheral leukocytes, the patient was initially diagnosed with "sporadic" XLAS. However, genetic analysis of the patient's sister with microscopic hematuria identified the same COL4A5 heterozygous mutation. Therefore, we concluded that our patient and the sister had XLAS caused by maternal germline mosaicism, not "sporadic" XLAS. Our case suggests that "sporadic" XLAS may in some patients be caused by the transmission of an abnormal allele from either parent with germline mosaicism in COL4A5. Germline mosaicism is thought to be rare, but we should consider that even asymptomatic parents of "sporadic" XLAS patients could carry a somatic and/or germline mosaicism. More cautious genetic counseling is advisable for all "sporadic" XLAS patients. Furthermore, urinalysis screening of "sporadic" XLAS patients' siblings is also important to enable an earlier detection of parental germline mosaicism. More... »

PAGES

1-5

References to SciGraph publications

  • 2017-10. Female X-linked Alport syndrome with somatic mosaicism in CLINICAL AND EXPERIMENTAL NEPHROLOGY
  • 2016. Inherited Glomerular Diseases in PEDIATRIC NEPHROLOGY
  • 2016-03. Somatic mosaicism and variant frequency detected by next-generation sequencing in X-linked Alport syndrome in EUROPEAN JOURNAL OF HUMAN GENETICS
  • 2016-04. Unrevealed mosaicism in the next-generation sequencing era in MOLECULAR GENETICS AND GENOMICS
  • 1998-04. Germ line mosaicism in HUMAN GENETICS
  • Journal

    TITLE

    Journal of Nephrology

    ISSUE

    N/A

    VOLUME

    N/A

    Author Affiliations

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s40620-018-0518-y

    DOI

    http://dx.doi.org/10.1007/s40620-018-0518-y

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1105911487

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30062677


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    129 schema:name Department of Pediatrics, Hokkaido University Graduate School of Medicine, North 15, West 7, 060-8638, Sapporo, Hokkaido, Japan
    130 rdf:type schema:Organization
     




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