原发性肉碱缺乏症患者临床特点和SLC22A5基因突变分析
温鹏强;陈占玲;王国兵;苏喆;万力生;崔冬;唐根;刘晓红;陈淑丽
【期刊名称】《中华内分泌代谢杂志》 【年(卷),期】2017(033)003
【摘要】Objective To investigate the clinical and biochemical metabolic features of 12 patients with systemic primary carnitine deficiency(CDSP) and to identify the SLC22A5 gene mutation types of the disease. Method The clinical and biochemical data were collected by retrospective analysis. DNA direct sequencing and multiplex ligation dependent probe amplification(MLPA)were applied for SLC22A5 gene analysis. Result Among 12 patients with CDSP, 3 cases had evident infection factors, 6 cases with convulsions, 5 cases manifested liver hypertrophy, 8 cases with hyperammonemia, and 9 cases showed myocardial damage. All CDSP patients were detected biallelic pathogenic mutation in SLC22A5 gene by direct sequencing. The gene types include IVS2+1G>T, c.3G>T(p.Met1Ile), c.760C>T(p.Arg254X), c.1400C>G(p.Ser467Cys),
c.844dupc(p.Arg282fs),
c.338G>A(p.Cys113Tyr), c.51C>G(p.Phe17Leu), c.659A>T(p.Glu220Val), and
c.1365dupC(p.Thr456fs).
c.659A>T(p.Glu220Val)
and
c.1365dupC(p.Thr456fs)are novel mutations. One female patient was maternal CDSP, her child had abnormal newborn screening. The allele frequency of c.760C>T(p.Arg254X) and c.1400C>G(p.Ser467Cys) were
37.5%(9/24)and 29.2%(7/24)respectively. The MLPA test results of all patients were negative. Conclusion The clinical manifestations are complex and various in patients with CDSP. Point and small InDel(insertions/deletions)mutation constitute the major alteration in SLC22A5 gene. c.1400C>G(p.Ser467Cys) might be another prevalence mutation type in Chinese CDSP patient.%目的 探讨12例原发性肉碱缺乏症患者临床表现与生化代谢特点,并分析其SLC22A5基因突变类型.方法 对12例患者病历资料进行回顾性分析;SLC22A5基因突变分析则采用PCR扩增产物直接测序法和多重连接探针扩增技术.结果 在12例患者中,3例有明显感染因素,6例患者临床表现有抽搐,5例患者表现有肝脏肿大,8例患者表现有高氨血症,9例表现有不同程度的心肌损害.12例患者通过DNA直接测序法检测出双等位基因致病突变,其基因突变类型有9种,包括:IVS2+1G>T、c.3G>T(p.Met1Ile)、c.760C>T(p.Arg254X)、c.1400C>G(p.Ser467Cys)、c.844dupc(p.Arg282fs)、c.338G>A(p.Cys113Tyr)、c.51C>G(p.Phe17Leu)、c.659A>T(p.Glu220Val)和c.1365dupC(p.Thr456fs).在检测到的9种基因突变类型中,c.659A>T(p.Glu220Val)和c.1365dupC(p.Thr456fs)为新发突变.1名病例为成年女性原发性肉碱缺乏症患者,其刚出生的新生儿筛查结果呈阳性.在检测到的基因突变类型中,c.760C>T(p.Arg254X)和c.1400C>G(p.Ser467Cys)等位基因频率最高,分别为37.5%(9/24)和29.2%(7/24).12例原发性肉碱缺乏症患者多重连接探针扩增技术检测结果未见异常.结论 原发性肉碱缺乏症患者临床表现复杂多样.SLC22A5基因突变类型以点突变为主,其中c.1400C>G(p.Ser467Cys)等位基因频率较高,也可能为中国原发性肉碱缺乏症
患者热点突变类型. 【总页数】7页(208-214)
【关键词】原发性肉碱缺乏症;SLC22A5;游离肉碱;酰基肉碱;多重连接探针扩增技术
【作者】温鹏强;陈占玲;王国兵;苏喆;万力生;崔冬;唐根;刘晓红;陈淑丽
【作者单位】518038 深圳市儿童医院儿科研究所;广东省东莞市人民医院内分泌科;518038 深圳市儿童医院儿科研究所;518038 深圳市儿童医院内分泌科;518038 深圳市儿童医院中医科;518038 深圳市儿童医院儿科研究所;518038 深圳市儿童医院儿科研究所;518038 深圳市儿童医院新生儿科;518038 深圳市儿童医院遗传代谢病专科 【正文语种】中文 【中图分类】 【文献来源】
https://www.zhangqiaokeyan.com/academic-journal-cn_chinese-journal-endocrinology-metabolism_thesis/0201232442922.html 【相关文献】
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2.原发性肉碱缺乏症的筛查与患者SLC22A5基因突变分析 [J], 王秀利; 顾茂胜; 杨丹艳; 索峰
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原发性肉碱缺乏症患者临床特点和SLC22A5基因突变分析
