PDF(Pubmed)
Abstract：
UNASSIGNED: CACNA1S related congenital myopathy is an emerging recently described entity. In this report we describe 2 sisters with mutations in the CACNA1S gene and the novel phenotype of congenital myopathy and infantile onset episodic weakness.
UNASSIGNED: Both sisters had neonatal onset hypotonia, muscle weakness, and delayed walking. Episodic weakness started in infancy and continued thereafter, provoked mostly by cold exposure. Muscle imaging revealed fat replacement of gluteus maximus muscles. Next generation sequencing found the missense p.Cys944Tyr variant and the novel splicing variant c.3526-2A>G in CACNA1S. Minigene assay revealed the splicing variant caused skipping of exon 28 from the transcript, potentially affecting protein folding and/or voltage dependent activation.
UNASSIGNED: This novel phenotype supports the notion that there are age related differences in the clinical expression of CACNA1S gene mutations. This expands our understanding of mutations located in regions of the CACNA1S outside the highly conserved S4 segment, where most mutations thus far have been identified.
UNASSIGNED: Both sisters had neonatal onset hypotonia, muscle weakness, and delayed walking. Episodic weakness started in infancy and continued thereafter, provoked mostly by cold exposure. Muscle imaging revealed fat replacement of gluteus maximus muscles. Next generation sequencing found the missense p.Cys944Tyr variant and the novel splicing variant c.3526-2A>G in CACNA1S. Minigene assay revealed the splicing variant caused skipping of exon 28 from the transcript, potentially affecting protein folding and/or voltage dependent activation.
UNASSIGNED: This novel phenotype supports the notion that there are age related differences in the clinical expression of CACNA1S gene mutations. This expands our understanding of mutations located in regions of the CACNA1S outside the highly conserved S4 segment, where most mutations thus far have been identified.
摘要：
■CACNA1S相关的先天性肌病是最近出现的一个实体。在本报告中，我们描述了2个CACNA1S基因突变的姐妹以及先天性肌病和婴儿发作性发作性无力的新表型。
■两姐妹都有新生儿张力减退,肌肉无力,耽误了走路。发作性虚弱始于婴儿期，此后一直持续，主要是由寒冷暴露引起的。肌肉成像显示臀大肌的脂肪替代。下一代测序在CACNA1S中发现了错义p.Cys944Tyr变体和新的剪接变体c.3526-2A>G。Minigene分析显示剪接变体导致转录本外显子28的跳跃，可能影响蛋白质折叠和/或电压依赖性激活。
■这种新的表型支持CACNA1S基因突变的临床表达存在年龄相关差异的观点。这扩展了我们对位于高度保守的S4片段之外的CACNA1S区域的突变的理解。到目前为止，大多数突变已经被鉴定出来。
■两姐妹都有新生儿张力减退,肌肉无力,耽误了走路。发作性虚弱始于婴儿期，此后一直持续，主要是由寒冷暴露引起的。肌肉成像显示臀大肌的脂肪替代。下一代测序在CACNA1S中发现了错义p.Cys944Tyr变体和新的剪接变体c.3526-2A>G。Minigene分析显示剪接变体导致转录本外显子28的跳跃，可能影响蛋白质折叠和/或电压依赖性激活。
■这种新的表型支持CACNA1S基因突变的临床表达存在年龄相关差异的观点。这扩展了我们对位于高度保守的S4片段之外的CACNA1S区域的突变的理解。到目前为止，大多数突变已经被鉴定出来。
