Dahan K, Heidet L, Zhou J, Mettler G, Leppig K A, Proesmans W, David A, Roussel B, Mongeau J G, Gould J M
INSERM U423, Hôpital Necker-Enfants Malades, Paris, France.
Kidney Int. 1995 Dec;48(6):1900-6. doi: 10.1038/ki.1995.489.
X-linked Alport syndrome (AS) associated with diffuse esophageal leiomyomatosis (DL) has been reported to be due to deletions removing the 5' ends of both the COL4A5 and COL4A6 genes, encoding the alpha 5 and alpha 6 chains of type IV collagen, respectively, whereas a variety of mutations in COL4A5 has been identified in patients with AS alone. Here we report three additional DL-AS patients who also display deletions removing the 5' ends of both COL4A5 and COL4A6 genes. Furthermore, we tracked the mutation in 15 females belonging to six DL-AS families by gene copy number determination. We found that, like AS, DL is transmitted as an X-linked dominant trait but, contrary to AS, DL is fully penetrant and completely expressed in females. These results are in agreement with our previous work suggesting that DL could be due to a dominant effect of an abnormal alpha 6 (IV) collagen chain. Finally, we have detected a similar deletion of the COL4A5 and COl4A6 genes in a DL affected female who showed no sign of nephropathy, demonstrating the AS carrier status of this DL patient. These results emphasize the importance of molecular analysis of female DL patients for genetic counseling.
据报道，与弥漫性食管平滑肌瘤病（DL）相关的X连锁Alport综合征（AS）是由于缺失分别编码IV型胶原α5和α6链的COL4A5和COL4A6基因的5'端，而在仅患有AS的患者中已鉴定出COL4A5的多种突变。在此，我们报告另外三名DL-AS患者，他们也表现出缺失COL4A5和COL4A6基因的5'端。此外，我们通过基因拷贝数测定追踪了六个DL-AS家族中15名女性的突变情况。我们发现，与AS一样，DL作为X连锁显性性状遗传，但与AS不同的是，DL在女性中完全显性且完全表现出来。这些结果与我们之前的研究结果一致，表明DL可能是由于异常的α6（IV）胶原链的显性效应所致。最后，我们在一名未表现出肾病迹象的DL受累女性中检测到COL4A5和COL4A6基因的类似缺失，证明该DL患者为AS携带者状态。这些结果强调了对女性DL患者进行分子分析以进行遗传咨询的重要性。
