Medical Genetics, University Hospital of Parma, 43126 Parma, Italy.
Medical Genetics, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy.
Genes (Basel). 2024 Jul 13;15(7):916. doi: 10.3390/genes15070916.
Leucine zipper-like transcription regulator 1 (LZTR1) acts as a negative factor that suppresses RAS function and MAPK signaling; mutations in this protein may dysregulate RAS ubiquitination and lead to impaired degradation of RAS superfamily proteins. Germline variants are reported in Noonan syndrome, either autosomal dominant or autosomal recessive, and in susceptibility to schwannomatosis. This article explores the genetic and phenotypic diversity of the autosomal dominant -related disorders, compiling a cohort of previously published patients (51 with the Noonan phenotype and 123 with schwannomatosis) and presenting two additional adult-onset cases: a male with schwannomatosis and Parkinson's disease and a female with Noonan syndrome, generalized joint hypermobility, and breast cancer. This review confirms that autosomal dominant -related disorders exhibit an extreme phenotypic variability, ranging from relatively mild manifestations to severe and multi-systemic involvement, and offers updated frequences of each clinical feature. The aim is to precisely define the clinical spectrum of -related diseases, using also two new emblematic clinical cases. Gaining insight into the mechanisms underneath this variability is crucial to achieve precision diagnostics and the development of therapeutic interventions.
亮氨酸拉链样转录调节因子 1（LZTR1）作为一种负调控因子，抑制 RAS 功能和 MAPK 信号通路；该蛋白的突变可能导致 RAS 泛素化失调，从而影响 RAS 家族蛋白的降解。LZTR1 种系变异可导致常染色体显性遗传或常染色体隐性遗传的诺南综合征和施万细胞瘤易感性。本文探讨了常染色体显性遗传相关疾病的遗传和表型多样性，汇集了先前发表的患者队列（51 名诺南综合征表型和 123 名施万细胞瘤），并介绍了另外两例成年发病的病例：一名男性患有施万细胞瘤和帕金森病，一名女性患有诺南综合征、全身关节过度活动和乳腺癌。本综述证实，常染色体显性遗传相关疾病表现出极端的表型变异性，从相对轻微的表现到严重和多系统受累不等，并提供了每种临床特征的最新频率。目的是使用两个新的标志性临床病例，精确定义相关疾病的临床谱。深入了解这种变异性背后的机制对于实现精准诊断和治疗干预至关重要。
