Document Detail

Somatic mosaicism for a mutation of the COL4A5 gene is a cause of mild phenotype male Alport syndrome.
MedLine Citation:
PMID:  18332068     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Alport syndrome is the most common form of hereditary nephritis and is mainly caused by mutations in the COL4A5 gene, which shows the X-linked form. It is well known that some male Alport syndrome cases show a relatively mild phenotype, but few molecular investigations have been conducted to clarify the mechanism of this phenotype. Methods and results. This report concerns an 8-year-old male sporadic Alport syndrome patient. While electron microscopy of the glomerular basement membrane showed typical findings for Alport syndrome, however, the immunohistochemical analysis of the glomerulus showed mosaic staining of the type IV collagen alpha 5 chain. The mutational analysis of the COL4A5 gene unexpectedly disclosed two peaks at the intron 43 splicing acceptor site (c. 3998-2 a/t) with direct sequencing. Restriction enzyme analysis demonstrated that the presence of somatic mosaicism was responsible for this mutation. mRNA extracted from the urinary sediments was analysed by RT-PCR and two PCR fragments were amplified, one consisting of a normal sequence and one with skipping of exon 44.
CONCLUSIONS: Our findings indicate that somatic mosaicism for COL4A5 is responsible for male X-linked Alport syndrome with an alpha 5 mosaic staining pattern. Several cases with somatic mosaicism have previously been reported, however, this is the first case where the presence of this mutation was proved with a comprehensive analysis of genomic DNA, mRNA and alpha 5 expression in the tissues. Somatic mosaicism may thus be one of the causes of the mild phenotype in Alport syndrome.
Rafal Przybyslaw Krol; Kandai Nozu; Koichi Nakanishi; Kazumoto Iijima; Yasuhiro Takeshima; Xue Jun Fu; Yoshimi Nozu; Hiroshi Kaito; Kyoko Kanda; Masafumi Matsuo; Norishige Yoshikawa
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Publication Detail:
Type:  Case Reports; Journal Article     Date:  2008-03-10
Journal Detail:
Title:  Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association     Volume:  23     ISSN:  1460-2385     ISO Abbreviation:  Nephrol. Dial. Transplant.     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-07-29     Completed Date:  2009-02-20     Revised Date:  2013-05-20    
Medline Journal Info:
Nlm Unique ID:  8706402     Medline TA:  Nephrol Dial Transplant     Country:  England    
Other Details:
Languages:  eng     Pagination:  2525-30     Citation Subset:  IM    
Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe 650-0017, Hyogo, Japan.
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MeSH Terms
Base Sequence
Chromosomes, Human, X / genetics
Collagen Type IV / genetics*,  metabolism
DNA / genetics
DNA Mutational Analysis
DNA Primers / genetics
Glomerular Basement Membrane / metabolism,  pathology
Hematuria / genetics
Kidney / metabolism,  pathology
Nephritis, Hereditary / genetics*,  metabolism,  pathology
Proteinuria / genetics
RNA, Messenger / genetics,  metabolism
Reg. No./Substance:
0/COL4A5 protein, human; 0/Collagen Type IV; 0/DNA Primers; 0/RNA, Messenger; 9007-49-2/DNA

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