Bacchelli B, Quaglino D, Gheduzzi D, Taparelli F, Boraldi F, Trolli B, Le Saux O, Boyd C D, Ronchetti I P
Biomedical Sciences Department, University of Modena and Reggio Emilia, Italy.
Mod Pathol. 1999 Dec;12(12):1112-23.
Skin biopsies of 18 healthy relatives of patients with pseudoxanthoma elasticum (PXE), belonging to six different recessive families, have been examined by optical and electron microscopy in order to determine morphologic alterations potentially useful for the identification of carriers of this genetic disorder. These morphologic features have been compared with those observed in the same tissue areas of eight PXE patients belonging to the same families, with six normal subjects, and to the carrier status of these apparently unaffected relatives as determined by haplotype analysis using informative markers surrounding the locus of the PXE gene on chromosome 16p. The dermis of all the relatives of PXE patients, established by haplotype analysis to be heterozygote carriers of a mutation in the PXE gene, exhibited several alterations very similar, although less severe, to those typical in PXE patients. Alterations were present in the reticular dermis and consisted of irregular-sized collagen bundles and elastic fibers; elastic fibers fragmented, cribriform, and mineralized; numerous fibroblasts, larger than normal, and subendothelial elastin in small vessels. Strikingly, none of these dermal changes were noted in an unaffected relative in one family who was identified as a noncarrier by haplotype analysis. Although many of these alterations are not specific for PXE, the presence of these morphologic changes in unaffected relatives of PXE patients indicates alterations in skin that could be diagnostic for carriers of a subclinical phenotype of PXE.
对18名弹性假黄瘤（PXE）患者的健康亲属进行了皮肤活检，这些亲属来自6个不同的隐性遗传家族，通过光学显微镜和电子显微镜进行检查，以确定可能有助于识别这种遗传病携带者的形态学改变。将这些形态学特征与来自同一家族的8名PXE患者、6名正常受试者相同组织区域中观察到的特征进行比较，并与这些明显未受影响亲属的携带者状态进行比较，后者通过使用16号染色体上PXE基因位点周围的信息性标记进行单倍型分析来确定。通过单倍型分析确定为PXE基因杂合突变携带者的所有PXE患者亲属的真皮，均表现出一些与PXE患者典型改变非常相似（尽管程度较轻）的改变。这些改变存在于网状真皮中，包括大小不规则的胶原束和弹性纤维；弹性纤维断裂、筛状和矿化；大量比正常大的成纤维细胞以及小血管内皮下弹性蛋白。引人注目的是，在一个家族中，通过单倍型分析被确定为非携带者的一名未受影响亲属中未发现这些真皮变化。虽然其中许多改变并非PXE所特有，但PXE患者未受影响亲属中存在这些形态学变化表明皮肤存在改变，这可能有助于诊断PXE亚临床表型的携带者。
