摘要：

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。

关键词: 脊髓小脑共济失调, 表型, 基因, 突变

Abstract:

Objective  To make the diagnosis for a patient presented with head tremor and cerebellar atrophy by integrating clinical features and accessory examination with genetic testing and to explore the interpretation of genetic testing results.  Methods  A 30-year-old male patient's medical information, clinical pheontype, family history and accessory examinations were collected. The next?generation sequencing (NGS) of exons in 3994 causative genes of Mendelian inheritance diseases and the family tree verification were carried out. China Human Phenotype Ontology (CHPO), Phenomizer, Ensembl and Online Mendelian Inheritance in Man (OMIM) database were used to interpret the genetic test results.  Results  The patient carried heterozygous mutation of spinocerebellar 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 c.4436C > T (p.Thr1479Ile) which was also seen in his mother. Phenotypic similarity analysis showed the patient's phenotype was correspond with the phenotype of SCA19, and the variation locus of KCND3 gene c.1057A > G was highly conservative with homologous gene in different species.  Conclusions  By means of the integration of clinical phenotype with the result of genetic test, KCND3 gene c.1057A > G (p.Ser353Gly) carried in the patient is the pathogenic mutation.

Key words: Spinocerebellar ataxias, Phenotype, Genes, Mutation