X-linked Alport syndrome:: Natural history in 195 families and genotype-phenotype correlations in males
X-linked Alport syndrome:: Natural history in 195 families and genotype-phenotype correlations in males
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DOI：
10.1681/asn.v114649
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发表时间：
2000-04-01
影响因子：
13.6
通讯作者：
Gubler, MC
中科院分区：
文献类型：
--
作者：
Jais, JP;Knebelmann, B;Gubler, MC
奥尔波特综合征 (AS) 是一种 IV 型胶原遗传性疾病，其特征是伴有进行性血尿性肾炎、听力丧失以及经常出现的眼部变化。 COL4A5 胶原蛋白基因突变是导致该疾病更常见的 X 连锁显性形式的原因。已观察到相当大的等位基因异质性。已经建立了“欧洲共同体阿尔波特综合征协调行动”，以准确描述 AS 表型并确定大量家族中的基因型-表型相关性。收集了涉及 329 个家庭的数据，其中 250 个家庭具有 X 连锁传播。介绍了属于 195 个 COL4A5 突变家族的 401 名男性患者的特征。所有男性患者均为血尿，进展至终末期肾衰竭和耳聋的速度与突变有关。大的缺失、无义突变或改变阅读框的小突变使受影响的男性患者在 30 岁之前有 90% 的可能性发生终末期肾衰竭，而在错义或剪接位点突变的患者中，同样的风险分别为 50% 和 70%。错义突变患者在 30 岁之前出现听力损失的风险约为 60%，而其他类型突变的患者则为 90%。 X 连锁 AS 的自然史以及与 COL4A5 突变的相关性已在一大群男性患者中建立。这些数据可用于进一步评估治疗方法。
Alport syndrome (AS) is a type IV collagen hereditary disease characterized by the association of progressive hematuric nephritis, hearing loss, and, frequently, ocular changes. Mutations in the COL4A5 collagen gene are responsible for the more common X-linked dominant form of the disease. Considerable allelic heterogeneity has been observed. A "European Community Alport Syndrome Concerted Action" has been established to delineate accurately the AS phenotype and to determine genotype-phenotype correlations in a large number of families. Data concerning 329 families, 250 of them with an X-linked transmission, were collected. Characteristics of the 401 male patients belonging to the 195 families with COL4A5 mutation are presented. All male patients were hematuric, and the rate of progression to end-stage renal failure and deafness was mutation-dependent. Large deletions, nonsense mutations, or small mutations changing the reading frame conferred to affected male patients a 90% probability of developing end-stage renal failure before 30 yr of age, whereas the same risk was of 50 and 70%, respectively, in patients with missense or splice site mutation. The risk of developing hearing loss before 30 yr of age was approximately 60% in patients with missense mutations, contrary to 90% for the other types of mutations. The natural history of X-linked AS and correlations with COL4A5 mutations have been established in a large cohort of male patients. These data could be used for further evaluation of therapeutic approaches.