Autosomal dominant Emery-Dreifuss dystrophy due to mutations in rod domain of the lamin A/C gene
Autosomal dominant Emery-Dreifuss dystrophy due to mutations in rod domain of the lamin A/C gene
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DOI：
10.1212/wnl.55.2.275
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发表时间：
2000-07-25
期刊：
影响因子：
9.9
通讯作者：
Grunnet, ML
中科院分区：
文献类型：
--
作者：
Felice, KJ;Schwartz, RC;Grunnet, ML
背景资料：常染色体显性Emery-Dreifuss型肌营养不良症（EDMD-AD）是一种临床上以肱骨骨盆无力、挛缩和心肌病为特征的疾病，遗传上以1q21.2-q21.3上的核纤层蛋白AIC基因突变为特征。在迄今为止报道的14个核纤层蛋白AIC基因突变中，涉及杆结构域的4个与孤立的心肌病和传导系统疾病相关。这是第一次报告杆结构域突变的患者与完整的EDMD-AD表型。研究方法：结果：在两个家系中，EDMD-AD的全部临床表现都得到了证实。对家系1的先证者，序列分析检测到核纤层蛋白A/C基因外显子2内的突变。错义突变是由于A448 C碱基替换导致Thr 150 Pro氨基酸改变。对于家族2的先证者，序列分析检测到外显子4的框内3-bp缺失（AAG 778-780或781-783），去除了两个相邻赖氨酸残基（K 260或261）中的一个。这两个突变都位于核纤层蛋白A/C基因的中心杆状结构域。结论：核纤层蛋白A/C基因杆状结构域的突变可能导致EDMD-AD的全临床谱。
Background: Autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD-AD) is a disorder characterized clinically by humeropelvic weakness, contractures, and cardiomyopathy, and genetically by mutations in the lamin AIC gene on 1q21.2-q21.3. Of the 14 lamin AIC gene mutations reported thus far, the four involving the rod domain have been associated with isolated cardiomyopathy and conduction-system disease. This is the first report of rod domain mutations in patients with the full EDMD-AD phenotype. Methods: Clinical, pathologic, and genetic data are provided on two families with EDMD-AD; Results: In both families, the full clinical spectrum of EDMD-AD was demonstrated. For the proband in family 1, sequence analysis detected a mutation within exon 2 of the lamin A/C gene. The missense mutation was due to a A448C base substitution causing a Thr150Pro amino acid change. For the proband of family 2, sequence analysis detected an in-frame 3-bp deletion (AAG 778-780 or 781-783) removing one of two adjacent lysine residues (K 260 or 261) of exon 4. Both mutations were in the central rod domain of the lamin A/C gene. Conclusions: Mutations in the rod domain of the lamin A/C gene may cause the full clinical spectrum of EDMD-AD.