Plomp Astrid S, Hu Xiaofeng, de Jong Paulus T V M, Bergen Arthur A B
The Netherlands Ophthalmic Research Institute, KNAW, Amsterdam, The Netherlands.
Am J Med Genet A. 2004 May 1;126A(4):403-12. doi: 10.1002/ajmg.a.20632.
Pseudoxanthoma elasticum (PXE) is a progressive disorder of elastic fibers in skin, eyes, and arterial walls. It is caused by mutations in the ABCC6 gene. Most patients are sporadic cases. The majority of familial cases show autosomal recessive (AR) inheritance, but autosomal dominant (AD) inheritance has also been reported. We reviewed the literature on AD PXE and we studied in detail, both clinically and by DNA studies, a selection of potentially AD pedigrees from our patient population consisting of 59 probands and their family members. Individuals were considered to have definite PXE if they had two of the following three criteria: characteristic ophthalmologic signs, characteristic dermatologic signs, and a positive skin biopsy. In the literature we found only three families with definite PXE in two successive generations and no families with definite PXE in three or more generations. Our own data set comprised three putative AD families. Extensive DNA studies revealed a mutation in only one ABCC6 allele in the patients of these families. Only one of our families showed definite PXE in two generations. Linkage studies revealed that pseudodominance was unlikely in this family. In the other two families AD PXE could not be confirmed after extensive clinical examinations and application of our criteria, since definite PXE was not present in two or more generations.
the inheritance pattern in PXE usually is AR. Part of the phenotype in family members of PXE patients might be due to expression in heterozygous carriers of an AR disease. AD inheritance in PXE may exist, but is both after careful literature study and in our patient material much rarer than previously thought.
弹性假黄瘤（PXE）是一种累及皮肤、眼睛和动脉壁弹性纤维的进行性疾病。它由ABCC6基因突变引起。大多数患者为散发病例。大多数家族性病例表现为常染色体隐性（AR）遗传，但也有常染色体显性（AD）遗传的报道。我们回顾了关于AD型PXE的文献，并对我们患者群体中59名先证者及其家庭成员中挑选出的一系列可能为AD遗传的家系进行了详细的临床和DNA研究。如果个体具备以下三个标准中的两个，则被认为患有确诊的PXE：特征性眼科体征、特征性皮肤病体征和皮肤活检阳性。在文献中，我们仅发现三个连续两代患有确诊PXE的家族，没有发现三代或更多代患有确诊PXE的家族。我们自己的数据集包含三个推定的AD家系。广泛的DNA研究显示，这些家系中的患者仅一个ABCC6等位基因发生了突变。我们的家族中只有一个在两代中表现出确诊的PXE。连锁研究表明，该家族不太可能出现假显性。在另外两个家族中，经过广泛的临床检查并应用我们的标准后，无法确诊AD型PXE，因为在两代或更多代中不存在确诊的PXE。
PXE的遗传模式通常为AR。PXE患者家庭成员的部分表型可能归因于AR疾病杂合携带者的表达。PXE中的AD遗传可能存在，但经过仔细的文献研究以及我们的患者资料表明，其比之前认为的要罕见得多。
