Kufor-Rakeb Syndrome/PARK9: One Novel and One Possible Recurring Ashkenazi ATP13A2 Mutation

被引：11

作者：

Inzelberg, Rivka ^{[1
,2
]}

Estrada-Cuzcano, Alejandro ^{[5
]}

Laitman, Yael ^{[6
]}

De Vriendt, Els ^{[5
]}

Friedman, Eitan ^{[3
,4
,6
]}

Jordanova, Albena ^{[5
]}

机构：

[1] Tel Aviv Univ, Dept Neurol, Tel Aviv, Israel

[2] Tel Aviv Univ, Dept Neurosurg, Tel Aviv, Israel

[3] Tel Aviv Univ, Sackler Fac Med, Dept Internal Med, Tel Aviv, Israel

[4] Tel Aviv Univ, Sackler Fac Med, Dept Genet & Biochem, Tel Aviv, Israel

[5] Univ Antwerp, VIB Ctr Mol Neurol, Mol Neurogen Grp, Antwerp, Belgium

[6] Sheba Med Ctr, Inst Human Genet, Susanne Levy Gertner Oncogenet Unit, Tel Hashomer, Israel

来源：

JOURNAL OF PARKINSONS DISEASE | 2018年 / 8卷 / 03期

关键词：

Parkinson's disease; Parkinsonism; Genetics; PARK9; Kufor-Rakeb syndrome; Ashkenazi; PYRAMIDAL DEGENERATION; PARKINSONISM; DISEASE; DEMENTIA; RISK;

D O I：

10.3233/JPD-181360

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：399 / 403

页数：5

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