Chassaing Nicolas, Martin Ludovic, Bourthoumieu Sylvie, Calvas Patrick, Hovnanian Alain
INSERM, U563, Centre de Physiopathologie de Toulouse Purpan, Toulouse, F-31300 France.
Hum Mutat. 2007 Oct;28(10):1046. doi: 10.1002/humu.9509.
Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder of connective tissues, which manifests with cutaneous, ophthalmologic and cardiovascular findings. PXE is caused by mutations in ABCC6 encoding a multidrug resistance protein (ABCC6, also known as MRP6). ABCC6 mutation detection rate ranges from 55% to 97% and it has been suggested that some of the remaining unidentified mutant alleles could correspond to large genomic rearrangements. In our cohort of 65 French PXE patients analysed for ABCC6 mutations, we identified two novel homozygous ABCC6 exonic deletions (deletions of exons 9-10 and exons 24-27). In order to systematically search for heterozygous genomic rearrangements, we have developed a quantitative multiplex PCR of short fluorescent fragments (QMPSF) approach that screens the 31 exons of ABCC6. We used QMPSF to analyse 13 PXE carrying at least one unidentified mutant, corresponding to 18 unidentified mutated alleles. This led to the detection of three large ABCC6 deletions, and two deletions of a single exon (exon 1 and exon 21). Thus QMPSF identified the causative mutation in 28% (5/18) of the uncharacterized ABCC6 mutant alleles in this cohort.
弹性假黄瘤（PXE）是一种常染色体隐性结缔组织疾病，表现为皮肤、眼科和心血管方面的症状。PXE由编码多药耐药蛋白（ABCC6，也称为MRP6）的ABCC6基因突变引起。ABCC6突变检测率在55%至97%之间，有人提出，其余一些未鉴定的突变等位基因可能对应于大的基因组重排。在我们对65名法国PXE患者进行ABCC6突变分析的队列中，我们鉴定出两个新的纯合ABCC6外显子缺失（外显子9 - 10和外显子24 - 27缺失）。为了系统地搜索杂合基因组重排，我们开发了一种短荧光片段定量多重PCR（QMPSF）方法，用于筛查ABCC6的31个外显子。我们使用QMPSF分析了13名携带至少一个未鉴定突变的PXE患者，对应18个未鉴定的突变等位基因。这导致检测到三个大的ABCC6缺失，以及两个单个外显子（外显子1和外显子21）的缺失。因此，QMPSF在该队列中28%（5/18）未表征的ABCC6突变等位基因中鉴定出了致病突变。
