J Parkinsons Dis. 2018;8(3):399-403. doi: 10.3233/JPD-181360.
Kufor-Rakeb syndrome (KRS)/PARK9 presents with autosomal recessive young onset Parkinson's disease (YOPD), spastic paraparesis, abnormal eye movements and facial myokymia. KRS is caused by homozygous/compound heterozygous inactivating mutations in ATP13A2. Two affected siblings (born to non-consanguineous Jewish parents) presenting a similar KRS phenotype (onset age 27, 23), carried compound heterozygous pathogenic variants in ATP13A2: c.217_218insG and c.3057delC. Allele frequency of the c.3057delC mutation was about 100 times higher in Ashkenazi controls in our study (1/190 = 0.00526) and in the Genome Aggregation Database, (GnomAD, 27/10132 = 0.002665) versus non-Ashkenazi controls worldwide in GnomAD (9/264566 = 0.000034018, p < 0.0001). The c.217_218insG mutation is novel and not found in controls or GnomAD. The c.3057delC mutation should be included in the genetic workup of Ashkenazi YOPD patients.
Kufor-Rakeb 综合征（KRS）/PARK9 表现为常染色体隐性早发性帕金森病（YOPD）、痉挛性截瘫、眼球运动异常和面部肌纤维抽搐。KRS 是由 ATP13A2 同源/复合杂合失活突变引起的。两名受影响的同胞（出生于非近亲犹太父母）表现出相似的 KRS 表型（发病年龄为 27 岁和 23 岁），携带 ATP13A2 的复合杂合致病性变异：c.217_218insG 和 c.3057delC。在我们的研究中，阿什肯纳兹对照（190 人中的 1 人，频率为 0.00526）和基因组聚集数据库（GnomAD，10132 人中的 27 人，频率为 0.002665）中，c.3057delC 突变的等位基因频率比全球非阿什肯纳兹对照高约 100 倍（264566 人中的 9 人，频率为 0.000034018，p<0.0001）。c.217_218insG 突变是新的，在对照或 GnomAD 中未发现。c.3057delC 突变应纳入阿什肯纳兹 YOPD 患者的基因检测中。
