A novel rearrangement of occludin causes brain calcification and renal dysfunction.

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  • Additional Information
    • Source:
      Publisher: Springer Verlag Country of Publication: Germany NLM ID: 7613873 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-1203 (Electronic) Linking ISSN: 03406717 NLM ISO Abbreviation: Hum Genet Subsets: MEDLINE
    • Publication Information:
      Publication: Berlin : Springer Verlag
      Original Publication: Berlin, New York, Springer-Verlag.
    • Subject Terms:
      Gene Rearrangement*; Brain/*physiopathology ; Calcinosis/*physiopathology ; Kidney/*physiopathology ; Occludin/*genetics; Canada ; Child, Preschool ; Chromosome Mapping ; DNA Copy Number Variations ; Exome ; Exons ; Female ; Gene Deletion ; Genotype ; Homozygote ; Humans ; Introns ; Malformations of Cortical Development/genetics ; Multiplex Polymerase Chain Reaction ; Mutation ; Occludin/metabolism ; Pedigree ; Phenotype ; Polymorphism, Single Nucleotide ; RNA Splicing ; Sequence Analysis, DNA
    • Abstract:
      Pediatric intracranial calcification may be caused by inherited or acquired factors. We describe the identification of a novel rearrangement in which a downstream pseudogene translocates into exon 9 of OCLN, resulting in band-like brain calcification and advanced chronic kidney disease in early childhood. SNP genotyping and read-depth variation from whole exome sequencing initially pointed to a mutation in the OCLN gene. The high degree of identity between OCLN and two pseudogenes required a combination of multiplex ligation-dependent probe amplification, PCR, and Sanger sequencing to identify the genomic rearrangement that was the underlying genetic cause of the disease. Mutations in exon 3, or at the 5-6 intron splice site, of OCLN have been reported to cause brain calcification and polymicrogyria with no evidence of extra-cranial phenotypes. Of the OCLN splice variants described, all make use of exon 9, while OCLN variants that use exons 3, 5, and 6 are tissue specific. The genetic rearrangement we identified in exon 9 provides a plausible explanation for the expanded clinical phenotype observed in our individuals. Furthermore, the lack of polymicrogyria associated with the rearrangement of OCLN in our patients extends the range of cranial defects that can be observed due to OCLN mutations.
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    • Grant Information:
      Canada Canadian Institutes of Health Research
    • Accession Number:
      0 (OCLN protein, human)
      0 (Occludin)
    • Publication Date:
      Date Created: 20130625 Date Completed: 20131202 Latest Revision: 20211021
    • Publication Date:
      20240829
    • Accession Number:
      10.1007/s00439-013-1327-y
    • Accession Number:
      23793442