Centronuclear myopathy due to a de novo dominant mutation in the skeletal muscle ryanodine receptor (RYR1) gene
Centronuclear myopathy due to a de novo dominant mutation in the skeletal muscle ryanodine receptor (RYR1) gene
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DOI：
10.1016/j.nmd.2007.01.016
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发表时间：
2007-04-01
影响因子：
2.8
通讯作者：
Muntoni, Francesco
中科院分区：
文献类型：
--
作者：
Jungbluth, Heinz;Zhou, Haiyan;Muntoni, Francesco
中心核肌病是一种遗传异质性的先天性肌病。虽然肌小管蛋白(MTM1)基因突变与X连锁变异有关，但动力蛋白2(DNM2)基因突变最近与显性遗传有关。我们报告一位16岁女孩，以先天性肌病和外眼肌麻痹为临床特征。在1年后的肌肉活检中，最显著的发现是多个中央核团影响多达50%的纤维和中心堆积的氧化酶染色。然而，8年后的重复活检中出现了一些核心样区；此外，肌肉MRI与我们之前在骨骼肌兰尼定受体(RYRI)基因突变患者中报道的模式是一致的。突变分析确定了一个新的显性RYRI错义突变(c.12335C>；T；Ser4112Leu)，影响蛋白质的一个高度保守的结构域。我们的发现扩大了与RYRI突变相关的表型谱，并表明在没有MTM1或DNM2突变的中心核肌病患者中应该考虑进行RYR1筛查；肌肉MRI可能有助于选择适当的基因测试。(C)2007 Elsevier B.V.保留所有权利。
Centronuclear myopathy is a genetically heterogeneous congenital myopathy. Whilst mutations in the myotubularin (MTM1) gene are implicated in the X-linked variant, mutations in the dynamin 2 (DNM2) gene have been recently associated with dominant inheritance. We report a 16-year-old girl with clinical features of a congenital myopathy and external ophthalmoplegia. Multiple central nuclei affecting up to 50% of fibres and central accumulation of oxidative enzyme stains were the most prominent findings on muscle biopsy obtained at 1 year. However, some core-like areas appeared on repeat biopsy 8 years later; in addition, muscle MRI was compatible with the pattern we previously reported in patients with mutations in the skeletal muscle ryanodine receptor (RYRI) gene. Mutational analysis identified a de novo dominant RYRI missense mutation (c.12335C > T; Ser4112Leu) affecting a highly conserved domain of the protein. Our findings expand the phenotypical spectrum associated with RYRI mutations and indicate that RYR1 screening should be considered in centronuclear myopathy patients without MTM1 or DNM2 mutations; muscle MRI may aid selection of appropriate genetic testing. (c) 2007 Elsevier B.V. All rights reserved.