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Alport syndrome caused by inversion of a 21 Mb fragment of the long arm of the X-chromosome comprising exon 9 through 51 of the COL4A5 gene

Hertz, J M; Persson, Ulf LU ; Juncker, I and Segelmark, Mårten LU (2005) In Human Genetics 118(1). p.23-28
Abstract
The X-linked form of Alport syndrome (AS) is caused by mutation in the COL4A5 gene located at Xq22.3 and encoding the alpha 5-chain of type IV-collagen. More than 400 different mutations have so far been detected in the COL4A5 gene. Not all mutations, however, will be detected using an exon-by-exon mutation detection strategy such as SSCP analysis or direct sequencing. We have previously reported the results of SSCP analysis of 81 patients suspected of X-linked AS. Genomic DNA from these 81 patients was also analyzed for larger genomic rearrangements, using Southern blotting analysis. Abnormal band patterns were found in three patients, two of which were caused by single base substitutions in the coding region, also detected by the SSCP... (More)
The X-linked form of Alport syndrome (AS) is caused by mutation in the COL4A5 gene located at Xq22.3 and encoding the alpha 5-chain of type IV-collagen. More than 400 different mutations have so far been detected in the COL4A5 gene. Not all mutations, however, will be detected using an exon-by-exon mutation detection strategy such as SSCP analysis or direct sequencing. We have previously reported the results of SSCP analysis of 81 patients suspected of X-linked AS. Genomic DNA from these 81 patients was also analyzed for larger genomic rearrangements, using Southern blotting analysis. Abnormal band patterns were found in three patients, two of which were caused by single base substitutions in the coding region, also detected by the SSCP analysis. Here we report the results of the analysis of a larger structural COL4A5 rearrangement that escaped the SSCP analysis. The rearrangement was found to be an inversion of a 21 Mb fragment of the COL4A5 gene comprising exon 9 through 51 with proximal breakpoint within intron 8 at Xq22.3 and a distal breakpoint 56 kb upstream to the initiation codon in the RAB33A gene at Xq25. The inversion of exon 9 through 51 is expected to result in a truncated or absent alpha 5(IV)chain and has not previously been associated with AS. These findings emphasize the need for a supplement to mutation detection strategies such as SSCP analysis and direct sequencing, in order to detect more complicated structural COL4A5 rearrangements. Larger structural rearrangements constitute 2.3% (1/43) of the mutations in the present material. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Human Genetics
volume
118
issue
1
pages
23 - 28
publisher
Springer
external identifiers
  • pmid:16133187
  • wos:000233338100003
  • scopus:33744728703
ISSN
1432-1203
DOI
10.1007/s00439-005-0013-0
language
English
LU publication?
yes
id
b6369eff-52d1-46be-9865-963c74edb9d0 (old id 213132)
date added to LUP
2007-08-03 09:26:52
date last changed
2017-01-01 07:04:33
@article{b6369eff-52d1-46be-9865-963c74edb9d0,
  abstract     = {The X-linked form of Alport syndrome (AS) is caused by mutation in the COL4A5 gene located at Xq22.3 and encoding the alpha 5-chain of type IV-collagen. More than 400 different mutations have so far been detected in the COL4A5 gene. Not all mutations, however, will be detected using an exon-by-exon mutation detection strategy such as SSCP analysis or direct sequencing. We have previously reported the results of SSCP analysis of 81 patients suspected of X-linked AS. Genomic DNA from these 81 patients was also analyzed for larger genomic rearrangements, using Southern blotting analysis. Abnormal band patterns were found in three patients, two of which were caused by single base substitutions in the coding region, also detected by the SSCP analysis. Here we report the results of the analysis of a larger structural COL4A5 rearrangement that escaped the SSCP analysis. The rearrangement was found to be an inversion of a 21 Mb fragment of the COL4A5 gene comprising exon 9 through 51 with proximal breakpoint within intron 8 at Xq22.3 and a distal breakpoint 56 kb upstream to the initiation codon in the RAB33A gene at Xq25. The inversion of exon 9 through 51 is expected to result in a truncated or absent alpha 5(IV)chain and has not previously been associated with AS. These findings emphasize the need for a supplement to mutation detection strategies such as SSCP analysis and direct sequencing, in order to detect more complicated structural COL4A5 rearrangements. Larger structural rearrangements constitute 2.3% (1/43) of the mutations in the present material.},
  author       = {Hertz, J M and Persson, Ulf and Juncker, I and Segelmark, Mårten},
  issn         = {1432-1203},
  language     = {eng},
  number       = {1},
  pages        = {23--28},
  publisher    = {Springer},
  series       = {Human Genetics},
  title        = {Alport syndrome caused by inversion of a 21 Mb fragment of the long arm of the X-chromosome comprising exon 9 through 51 of the COL4A5 gene},
  url          = {http://dx.doi.org/10.1007/s00439-005-0013-0},
  volume       = {118},
  year         = {2005},
}