PDF(Pubmed)
Abstract：
BACKGROUND: The Triggering Receptor Expressed on Myeloid Cells 2 protein (TREM2) plays a crucial role in various biological processes, including osteoclast differentiation, and disease-associated microglia (DAM) activation to regulate neuroinflammation, and phagocytosis in the brain. Genetic variations in TREM2 are implicated in neurodegenerative disorders, such as Nasu-hakola disease (NHD), characterized by bone lesions, neuropsychiatric disorders, and early-onset dementia.
METHODS: We studied 3 siblings with suspected NHD. Whole-exome sequencing was conducted on the proband to identify the possible genetic cause(s) and by Sanger sequencing to validate the identified variants in the two other affected siblings, a healthy sister, and the parents.
RESULTS: We identified a novel homozygous deletion (c.549del; p.(Leu184Serfs*5)) in TREM2. Our literature review reveals 16 TREM2 mutations causing early-onset dementia and bone lesions.
CONCLUSIONS: These findings, alongside previous research, elucidate the clinical spectrum of TREM2-related diseases, aiding accurate diagnosis and patient care. This knowledge is vital for understanding TREM2-dependent DAM and its involvement in the pathogenesis of neurodevelopmental disorders which can help to develop targeted therapies and improve outcomes for TREM2-affected individuals.
METHODS: We studied 3 siblings with suspected NHD. Whole-exome sequencing was conducted on the proband to identify the possible genetic cause(s) and by Sanger sequencing to validate the identified variants in the two other affected siblings, a healthy sister, and the parents.
RESULTS: We identified a novel homozygous deletion (c.549del; p.(Leu184Serfs*5)) in TREM2. Our literature review reveals 16 TREM2 mutations causing early-onset dementia and bone lesions.
CONCLUSIONS: These findings, alongside previous research, elucidate the clinical spectrum of TREM2-related diseases, aiding accurate diagnosis and patient care. This knowledge is vital for understanding TREM2-dependent DAM and its involvement in the pathogenesis of neurodevelopmental disorders which can help to develop targeted therapies and improve outcomes for TREM2-affected individuals.
摘要：
背景：髓系细胞上表达的触发受体2蛋白（TREM2）在各种生物学过程中起着至关重要的作用，包括破骨细胞分化，和疾病相关的小胶质细胞（DAM）激活来调节神经炎症，和大脑中的吞噬作用。TREM2的遗传变异与神经退行性疾病有关，例如Nasu-hakola病（NHD），以骨病变为特征，神经精神疾病,和早发性痴呆.
方法：我们研究了3名疑似NHD的兄弟姐妹。对先证者进行全外显子组测序以确定可能的遗传原因，并通过Sanger测序以验证另外两个受影响的兄弟姐妹中已识别的变体。一个健康的妹妹,还有父母.
结果:我们在TREM2中鉴定了新的纯合缺失(c.549del;p.(Leu184Serfs*5))。我们的文献综述揭示了16个TREM2突变导致早发性痴呆和骨病变。
结论：这些发现，除了先前的研究，阐明TREM2相关疾病的临床谱，帮助准确的诊断和病人护理。这些知识对于理解TREM2依赖性DAM及其参与神经发育障碍的发病机理至关重要，这可以帮助开发靶向治疗并改善受TREM2影响的个体的结果。
方法：我们研究了3名疑似NHD的兄弟姐妹。对先证者进行全外显子组测序以确定可能的遗传原因，并通过Sanger测序以验证另外两个受影响的兄弟姐妹中已识别的变体。一个健康的妹妹,还有父母.
结果:我们在TREM2中鉴定了新的纯合缺失(c.549del;p.(Leu184Serfs*5))。我们的文献综述揭示了16个TREM2突变导致早发性痴呆和骨病变。
结论：这些发现，除了先前的研究，阐明TREM2相关疾病的临床谱，帮助准确的诊断和病人护理。这些知识对于理解TREM2依赖性DAM及其参与神经发育障碍的发病机理至关重要，这可以帮助开发靶向治疗并改善受TREM2影响的个体的结果。
