Lesch-nyhan综合征1例报道——来自HGPRT基因突变的中国家庭
Lesch-Nyhan syndrome in a Chinese family with mutation in the HGPRT gene
黄佼 1陈宇 1张楚 1郭钦贤 1张险峰 2马丽珍 1詹宇红1
作者信息
- 1. 杭州市第一人民医院,南京医科大学附属杭州医院 内分泌风湿免疫科,浙江 杭州 310006
- 2. 杭州市第一人民医院, 南京医科大学附属杭州医院 中心实验室,浙江 杭州 310006
- 折叠
摘要
Lesch-nyhan综合征(Lesch-Nyhan syndrome, LNS)是次黄嘌呤鸟嘌呤磷酸核糖转移酶(hypoxanthine guanine phosphoribosyl transferase, HGPRT)基因突变导致的一种先天性遗传病,该病由缺乏HGPRT酶引起.主要临床症状包括高尿酸血症、幼年型痛风性关节炎和神经系统发育障碍.相关研究报道了超过400个HPRT基因的突变位点,但Lesch-nyhan综合征在中国人口的发病率极低.本研究报道了一个16岁的伴有神经功能障碍和幼年型痛风性关节炎的男性患者,通过从外周血淋巴细胞中提取患者及其家族成员的DNA,并采用标准方法对HPRT基因的编码区和内含子-外显子侧翼进行测序,发现患者和他的母亲的HPRT基因的外显子3突变(Exon3:c.143G> A),导致编码蛋白质中的精氨酸被组氨酸(p.R48H)取代,在红细胞中没有检测到酶的活性.目前,有研究报道了在几个欧洲家庭中存在相同的突变,但首次在中国家庭中发现.由于该病在中国的发病率低,因而临床医师在诊断LNS病例方面的经验不足.因此,应对高尿酸血症、痛风性关节炎和神经功能障碍的婴儿或青少年进行LNS筛查.
Abstract
Lesch-Nyhan syndrome(LNS) is a congenital X-linked recessive inherited disorder caused by mutations in the hypoxanthine guanine phosphoribosyl transferase (HPRT) gene.A deficiency of the HPRT enzyme is responsible for the disease.The main clinical manifestation includes hyperuricemia, juvenile-onset gouty arthritis and neurological developmental disorders.Studies have reported there are more than 400 HPRT gene mutation sites, but the incidence of LNS in the Chinese population is extremely low.Here we report a 16-year-old male patient who suffered neurological dysfunction at an early age and gouty arthritis in his youth.DNA of patient and his family members were extracted from peripheral blood lymphocytes.The coding region and the intron-exon boundaries of HPRT gene were sequenced by standard methods.We found a mutation in exon 3 of the HPRT gene of the patient and his mother (Exon3:c.143G>A), which resulted in an arginine to histidine (p.R48H) substitution in the encoded protein.No activity of the enzyme HPRT was detected in the erythrocytes.The same mutation was reported in several European families, but was found in Chinese family for the first time.Clinicians in China have poor experience in diagnosing LNS case, due to the low incidence in China.Therefore LNS screening for infants or adolescents with hyperuricemia, gouty arthritis and neurological dysfunction should be performed.
关键词
Lesch-nyhan综合征(LNS)/次黄嘌呤鸟嘌呤磷酸核糖转移酶(HGPRT)/高尿酸血症/基因突变Key words
Lesch-Nyhan syndrome (LNS)/hypoxanthine guanine phosphoribosyl transferase (HGPRT)/hyperuricemia/gene mutation引用本文复制引用
基金项目
浙江省医药卫生科技计划项目(2012KYB149)
出版年
2017
NETL
NSTL
维普
万方数据