| 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 |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
Rafal Przybyslaw Krol; Kandai Nozu; Koichi Nakanishi; Kazumoto Iijima; Yasuhiro Takeshima; Xue Jun Fu; Yoshimi Nozu; Hiroshi Kaito; Kyoko Kanda; Masafumi Matsuo; Norishige Yoshikawa |
Related Documents
:
|
12119278 - Role of pten, a lipid phosphatase upstream effector of protein kinase b, in epithelial ... 14564668 - Maspardin is mutated in mast syndrome, a complicated form of hereditary spastic paraple... 12682338 - Reversion of mtdna depletion in a patient with tk2 deficiency. 18001468 - Mutation analysis of the nsd1 gene in patients with autism spectrum disorders and macro... 21301768 - Laparoscopic duodenojejunostomy omega loop with braun anastomosis as a treatment for su... 18490618 - The als/pdc syndrome of guam and the cycad hypothesis. |
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: - |
Medline Journal Info:
|
Nlm Unique ID: 8706402 Medline TA: Nephrol Dial Transplant Country: England |
Other Details:
|
Languages: eng Pagination: 2525-30 Citation Subset: IM |
Affiliation:
|
Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe 650-0017, Hyogo, Japan. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Base Sequence Child Chromosomes, Human, X / genetics Collagen Type IV / genetics*, metabolism DNA / genetics DNA Mutational Analysis DNA Primers / genetics Exons Glomerular Basement Membrane / metabolism, pathology Hematuria / genetics Humans Kidney / metabolism, pathology Male Mosaicism* Mutation Nephritis, Hereditary / genetics*, metabolism, pathology Phenotype Proteinuria / genetics RNA, Messenger / genetics, metabolism |
| Chemical | |
Reg. No./Substance:
|
0/COL4A5 protein, human; 0/Collagen Type IV; 0/DNA Primers; 0/RNA, Messenger; 9007-49-2/DNA |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: HLA-DQ3 is a probable risk factor for CMV infection in high-risk kidney transplant patients.
Next Document: Outcomes of a provincial home haemodialysis programme--a two-year experience: establishing benchmark...