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解读DST相关疾病:影响DST-b的双变体会导致先天性肌肉病变

Maureen Jacob¹, Heike Kölbel², Philip Harrer^1,3

¹Institute of Human Genetics, School of Medicine and Health, Technical University of Munich, Munich 81675, Germany.

Brain : a journal of neurology

|June 11, 2025

概括

在DST基因中单独影响DST-b的双变异会导致先天性肌肉病变. 影响DST-a和DST-b的变种导致严重的,致命的先天性收缩综合征,扩大DST.

科学领域:

遗传学遗传学是一个
分子生物学分子生物学
神经学神经学

背景情况:

迪斯托宁 (DST) 基因编码了三个异型:DST-a,DST-b和DST-e.
DST中的致病变体与遗传性感官和自主神经病变类型VI (DST-a) 和表皮溶解牛简体3 (DST-e) 相关.
先天性肌肉病症代表了一组异构的神经肌肉疾病,在出生时出现.

研究的目的:

调查DST基因变异在先天性肌肉病变的作用.
为了识别受新型变异影响的特定DST异型.
为了确定DST相关疾病的基因型-表型相关性.

主要方法:

在受影响的个体中,整体外基因组或基因组测序.
在患者衍生细胞中进行RNA和蛋白质分析.
肌肉活检和超结构分析.
基因型-表型与现有文献的相关性.

主要成果:

九个新的双变体在40-41号外显子中,特定于DST-b,在19名患有重症新生儿肌病,关节,低血压和扩张心肌病的患者中被发现.
其中七名患者在三年内死亡;幸存者表现出症状改善与正常的认知和行走.
四名患有同卵性变异影响DST-a和DST-b的患者呈现出严重的关节和子宫内或新生儿死亡,定义为致命的先天性契合综合征.
DST-b变异主要影响骨肌肉和心脏,与观察到的表型相关.
肌肉活检显示了轻度,非特异性的肌肉病变和焦点肌纤维细胞干扰.

结论:

单独影响DST-b的双变体会导致具有不同严重性的自体逆性先天性肌肉病变.
影响DST-a和DST-b的变种导致更严重,致命的先天性契合综合征.
在DST内部的变异位置允许表型预测,支持将DST重新定义为具有四种不同的表型的疾病相关基因.

关键词:

在 DST 中使用 DST.心肌病性心脏病 - 心肌病性心脏病它们是异构体.骨髓病变是一种神经病变.神经遗传学神经遗传学神经肌肉疾病神经肌肉疾病

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