头部震颤伴小脑萎缩一例临床表型及基因突变分析

Clinical phenotype and genetic mutation of one case with head tremor and cerebellar atrophy

目的通过对1例头部震颤伴小脑萎缩患者临床表型和基因检测结果进行综合分析,明确诊断疾病并探讨基因检测结果的解读方法。方法与结果采集1例30岁男性患者临床表型,进行二代基因测序和Sanger测序验证,通过中文人类表型标准用语、基因检索工具Phenomizer、Ensembl数据库、在线人类孟德尔遗传数据库相关信息,对基因检测结果进行解读。结果显示,患者存在脊髓小脑共济失调19型(SCA19型)致病基因KCND3基因杂合突变c.1057A>G(p.Ser353Gly),其父母均未携带该突变基因;患者还存在帕金森病20型致病基因SYNJ1基因杂合突变c.4436C>T(p.Thr1479Ile),其母携带该突变基因。表型相似度分析显示,患者表型与SCA19型一致,KCND3基因变异位点c.1057A>G在不同物种同源基因中具有高度保守性。结论通过对患者临床表型和基因检测结果综合分析,KCND3基因杂合突变c.1057A>G(p.Ser353Gly)为致病性突变。

Objective To make the diagnosis for a patient presented with head tremor and cerebellar atrophy by integrating elinical features and aeeessory examination with genetic testing and to explore the interpretation of genetie testing results. Methods A 30-year-old male patient＇s medical information, clinical pheontype, family history and accessory examinations were co]leeted. The next-generation sequencing （NGS） of exons in 3994 causative genes of Mendelian inheritanee diseases and the family tree verification were carried out. China Human Phenotype Ontology （CHPO）, Phenomizer, Ensembl and Online Mendelian Inheritanee in Man （OMIM） database were used to interpret the genetie test results. Results The patient carried heterozygous mutation of spinoeerebellar ataxia type 19 （SCA19） related KCND3 gene c.1057A 〉 G （p. Ser353Gly）, but his parents did not carry this mutation. The patient also carried heterozygous mutation of parkinsonism type 20 （PARK20） related SYNJ1 gene e.4436C 〉 T （p.Thr1479Ile） which was also seen in his mother. Phenotypie similarity analysis showed the patient＇s phenotype was correspond with the phenotype of SCA19, and the variation loeus of KCND3 gene e.1057A 〉 G was highly conservative with homologous gene in different species. Conclusions By means of the integration of elinical phenotype with the result of genetic test, KCND3 gene e.lO57A 〉 G （p.Ser353Gly） earried in the patient is the pathogenic mutation.