Kufor-Rakeb Syndrome/PARK9: One Novel and One Possible Recurring Ashkenazi ATP13A2 Mutation.
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.
['Inzelberg|Rivka|R|', 'Estrada-Cuzcano|Alejandro|A|', 'Laitman|Yael|Y|', 'De Vriendt|Els|E|', 'Friedman|Eitan|E|', 'Jordanova|Albena|A|']
D000293:Adolescent D000328:Adult D017668:Age of Onset D002648:Child D005260:Female D006801:Humans D008297:Male D009154:Mutation D020734:Parkinsonian Disorders D010641:Phenotype D006180:Proton-Translocating ATPases D035781:Siblings D055815:Young Adult
Kufor-Rakeb syndrome PARK9 Ashkenazi Parkinsonism Genetics Parkinson’s disease