Colby Samantha, Yehia Lamis, Niazi Farshad, Chen JinLian, Ni Ying, Mester Jessica L, Eng Charis
Genomic Medicine Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA;; Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA;; Case Western Reserve University School of Medicine, Cleveland, Ohio 44195, USA.
Genomic Medicine Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA;; Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA;; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
Cold Spring Harb Mol Case Stud. 2016 Nov;2(6):a001230. doi: 10.1101/mcs.a001230.
Lhermitte-Duclos disease (LDD) is a rare cerebellar disorder believed to be pathognomonic for Cowden syndrome. Presently, the only known etiology is germline mutation. We report a 41-yr-old white female diagnosed with LDD and wild-type for . Exome sequencing revealed a germline heterozygous mutation that breaks a disulfide bond in the receptor's extracellular domain, resulting in constitutive activation. Functional studies demonstrate activation of ERK/AKT signaling pathways, mimicking loss-of-function downstream effects. The identification of as a candidate LDD susceptibility gene contributes to advancement of molecular diagnosis and targeted therapy for this rare condition with limited treatment options.
Lhermitte-Duclos病（LDD）是一种罕见的小脑疾病，被认为是考登综合征的特征性表现。目前，唯一已知的病因是种系突变。我们报告了一名41岁的白人女性，被诊断为LDD且 为野生型。外显子组测序发现了一个种系杂合突变，该突变破坏了受体细胞外结构域中的二硫键，导致组成性激活。功能研究表明ERK/AKT信号通路被激活，模拟了功能丧失的下游效应。将 鉴定为LDD候选易感基因有助于推进这种治疗选择有限的罕见疾病的分子诊断和靶向治疗。
