Guo Miao, Chen Yucai, Lin Longlong, Wang Yilin, Wang Anqi, Yuan Fang, Wang Chunmei, Wang Simei, Zhang Yuanfeng
Department of Neurology, Shanghai Children's Hospital, School of medicine, Shanghai Jiao Tong University, Shanghai, China.
Child Neurol Open. 2022 Jul 19;9:2329048X221108821. doi: 10.1177/2329048X221108821. eCollection 2022 Jan-Dec.
Lesch-Nyhan disease (LND) is a rare x-linked purine metabolic neurogenetic disease caused by enzyme hypoxanthine-guanine phosphoriribosyltransferase(HGprt) deficiency, also known as self-destructive appearance syndrome. A series of manifestations are caused by abnormal purine metabolism. The typical clinical manifestations are hyperuricemia, growth retardation, mental retardation, short stature, dance-like athetosis, aggressive behavior, and compulsive self-harm. We identified a point mutation c.151C > T (p. Arg51*) in a pedigree. We analyzed the clinical characteristics of children in a family, and obtained the blood of their parents and siblings for second-generation sequencing. At the same time, we also analyzed and compared the expression of HPRT1 gene and predicted the three-dimensional structure of the protein. And we analyzed the clinical manifestations caused by the defect of the HPRT1 gene. The mutation led to the termination of transcription at the 51st arginine, resulting in the production of truncated protein, and the relative expression of HPRT1 gene in patients was significantly lower than other family members and 10 normal individuals. This mutation leads to the early termination of protein translation and the formation of a truncated HPRT protein, which affects the function of the protein and generates corresponding clinical manifestations.
莱施-奈恩综合征（LND）是一种罕见的X连锁嘌呤代谢神经遗传性疾病，由次黄嘌呤-鸟嘌呤磷酸核糖转移酶（HGprt）缺乏引起，也称为自毁容貌综合征。一系列表现是由嘌呤代谢异常所致。典型的临床表现为高尿酸血症、生长发育迟缓、智力低下、身材矮小、舞蹈样手足徐动症、攻击性行为和强迫性自残。我们在一个家系中鉴定出一个点突变c.151C>T（p.Arg51*）。我们分析了一个家庭中患儿的临床特征，并获取其父母及兄弟姐妹的血液进行二代测序。同时，我们还分析比较了HPRT1基因的表达情况并预测了该蛋白的三维结构。并且我们分析了HPRT1基因缺陷所导致的临床表现。该突变导致转录在第51位精氨酸处终止，产生截短蛋白，患者中HPRT1基因的相对表达明显低于其他家庭成员及10名正常个体。这种突变导致蛋白质翻译提前终止并形成截短的HPRT蛋白，影响蛋白功能并产生相应的临床表现。
