家族性扩张型心肌病：临床和免疫遗传学异质性的证据。

Bilińska Zofia T, Michalak Ewa, Piatosa Barbara, Grzybowski Jacek, Skwarek Mirosław, Deptuch Tomasz W, Kuśmierczyk-Droszcz Beata, Piotrowski Walerian, Ruzyłło Witold

Department of General Cardiology, Institute of Cardiology, Warsaw, Poland.

Med Sci Monit. 2003 May;9(5):CR167-74.

BACKGROUND

There is increasing awareness of the familial nature of dilated cardiomyopathy (DCM). Mutations in the genes coding for cytoskeletal and sarcomere proteins have been identified. Phenotyping of familial DCM (FDCM) may help to improve genetic diagnosis. The aim of our study was to evaluate the clinical features, pattern of transmission, and immunogenetic data of FDCM.

MATERIAL/METHODS: We obtained family histories in order to construct pedigrees and prospectively evaluated 204 family members of 27 patients with angiographically proven DCM. FDCM was defined as more than 1 person with DCM in a family. The study protocol included repeated clinical examination, electrocardiography, echocardiography and blood sampling.

RESULTS

Among the families, we identified the following phenotypes: DCM with conduction defects (n=2), early onset DCM with a rapid course in male relatives (n=2), and DCM preceded by ventricular arrhythmia (n=1). The remaining families presented with a heterogeneous course of the disease. The disease was transmitted in an autosomal dominant fashion in 14 of our pedigrees, possibly X-linked in three and indeterminate in 10 sib-pairs. The frequency of the DRB104 allele was low in probands with the disease (3/20, 15%); heterozygozity for DRB103/DRB1*04, known to increase susceptibility to IDDM1, was identified in 2 of 20 DCM probands (10%).

CONCLUSIONS

Familial dilated cardiomyopathy is a heterogeneous disorder; autosomal dominant transmission is most common. The distinct clinical phenotypes and specific immunogenetic features found in some families indicate that different pathogenetic mechanisms can lead to the

背景

人们越来越意识到扩张型心肌病（DCM）具有家族性。已确定编码细胞骨架和肌节蛋白的基因突变。家族性扩张型心肌病（FDCM）的表型分析可能有助于改善基因诊断。我们研究的目的是评估FDCM的临床特征、遗传模式和免疫遗传学数据。

材料/方法：我们获取家族病史以构建家系，并对27例经血管造影证实为DCM患者的204名家庭成员进行前瞻性评估。FDCM定义为一个家族中有超过1人患有DCM。研究方案包括重复的临床检查、心电图、超声心动图和血液采样。

结果

在这些家族中，我们确定了以下表型：伴有传导缺陷的DCM（n = 2）、男性亲属中早发且病程进展迅速的DCM（n = 2）以及室性心律失常先于DCM出现（n = 1）。其余家族呈现出疾病的异质性病程。在我们的14个家系中，疾病以常染色体显性方式遗传，3个可能为X连锁，10个同胞对的遗传方式不确定。患病先证者中DRB104等位基因频率较低（3/20，15%）；在20例DCM先证者中有2例（10%）检测到已知会增加IDDM1易感性的DRB103/DRB1*04杂合性。