对于LZTR1中的功能丧失变体的异构性与孤立的多个咖啡馆-au-lait斑点有关
Gioia Mastromoro1, Claudia Santoro2, Marialetizia Motta3
1Medical Genetics Division, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy; Department of Experimental Medicine, Policlinico Umberto I Hospital, Sapienza University of Rome, Rome, Italy.
概括
在LZTR1的遗传变异与swanomatosis和Noonan综合征有关. 这项研究发现,这些LZTR1变异也会导致孤立的多个咖啡牛奶斑块 (CaLMs),扩大已知的疾病关联.
科学领域:
- 遗传学 是一个遗传学.
- 皮肤病学 皮肤病学
- 在瘤学瘤学.
背景情况:
- 致病性LZTR1变体是已知的斯瓦诺马托斯和诺南综合征 (NS) 的原因.
- 单独的多重咖啡牛奶斑块 (CaLMs) 的遗传基础尚未完全理解,特别是对于NF1和SPRED1变体负的病例.
研究的目的:
- 调查异合体功能丧失LZTR1等位基因与分离的多个CaLMs之间的关联.
- 在患有CaLMs的个体中描述LZTR1变异的临床和分子谱.
主要方法:
- 在849名具有多个CaLMs的参与者身上进行了RASopathy基因面板测序,不包括NF1和SPRED1致病变体.
- 收集了125名具有异性LZTR1变体的个体的临床数据和分子发现.
- 在选择的LZTR1变体上进行了体外功能评估.
主要成果:
- 在6.0%患有CaLMs.的参与者中发现了异构LZTR1变异.
- 与LZTR1相关的CaLMs表现出可变的呈现,有时具有RASopathy特征; schwannomas在2个家族中同时发生.
- 功能性研究显示,LZTR1变异导致蛋白质降解/错位化和MAPK信号受损.
结论:
- LZTR1变异与分离的多个CaLMs相关,扩大已知的表型谱.
- 这一发现涉及LZTR1在一个更广泛的条件范围超越s schwannomatosis和诺南综合征.
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