酪氨酸羟化酶基因新突变导致多巴反应性肌张力障碍家系分析  

Analysis of a Pedigree with Dopa-responsive Dystonia Caused by Novel Mutation of TH Gene

作　　者：段丽芬[1] 王惠萍[1] 孙莹[1] 王春霞[1] 王左华 张霞 沈茹[2] DUAN Li-fen;WANG Hui-ping;SUN Ying;WANG Chun-xia;WANG Zuo-hua;ZHANG Xia;SHEN Ru(Department of Pediatric neurology,Kunming Children's Hospital,Kunming 650228,China;Department of laboratory,Kunming Children's Hospital,Kunming 650228,China)

机构地区：[1]昆明市儿童医院神经内科,云南昆明650228 [2]昆明市儿童医院检验科,云南昆明650228

出　　处：《中山大学学报（医学版）》2019年第4期598-603,共6页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：云南省科技厅重点研发计划-国际科技合作专项(2018IA047);昆明市卫生科技人才培养项目(SW后备-86);昆明市科技保障民生发展计划项目(2019KJJH147)

摘　　要：【目的】研究多巴反应性肌张力障碍(DRD)家系TH基因突变特点。【方法】提取先证者及其父母和两个姐姐外周血基因组DNA,使用高通量测序(NGS)的方法对已知肌张力及运动障碍相关的256个致病基因进行检测。【结果】家系中2例患者(先证者和其大姐)的酪氨酸羟化酶(TH)基因外显子14、9存在c.1481C>T(p.Thr494Met)、c.943G>A(p.Gly315Ser)复合杂合突变,父母分别携带一个杂合突变,其表型正常的二姐和50名正常对照者均未检测到该突变。【结论】TH基因c.1481C>T(p.Thr494Met)、c.943G>A(p.Gly315Ser)突变导致了该DRD家系的基因异常,并且发现了新的TH基因突变,扩展了DRD基因型与临床表型的关系谱,对DRD的早期精准诊断和治疗是改善预后的关键。【Objective】To study the mutation characteristics of Tyrosine hydroxyls(TH)gene in a pedigree with dopa-responsive dystonia(DRD).【Methods】Extraction of genomic DNA from peripheral blood of a proband and his parents and two sisters using high-throughput sequencing(NGS)method were detected on 256 known pathogenicity genes associated with dystonia and dyskinesia.【Results】Mutations on tyrosine hydroxylase(TH)gene in the exon 14 and exon 9 were detected in the proband and his eldest sister in this pedigree.They had a complex heterozygosity of c.1481C > T(p.Thr494Met)and c.943G >A(p.Gly315Ser),and one heterozygous mutation was carried by parents respectively. The mutation was not detected in his second sister and 50 people with normal phenotype controls.【Conclusion】The mutations of TH gene c.1481C > T(p.Thr494Met)and c.943G > A(p.Gly315Ser)led to the gene abnormality in DRD family,and a new mutation of TH gene was found,which expanded the relationship between DRD genotype and clinical phenotype.It is vital that early accurate diagnosis and treatment of DRD is the key to improve prognosis.

关 键 词：多巴反应性肌张力障碍 酪氨酸羟化酶基因 高通量测序 三磷酸鸟苷环化水解酶1 

分 类 号：R725[医药卫生—儿科]