Parkinson's disease with homozygous PINK1 p.Leu489Pro mutations in two Indian sisters

• Main Authors: Lim, Shen-Yang, Ahmad-Annuar, Azlina, Lohmann, Katja, Tan, Ai Huey, Tay, Yi Wen, Lim, Jia Lun, Ramli, Norlisah, Teh, Pei Chiek, Kuppusamy, Rishikesan, Tan, Chong Tin, Goh, Khean Jin, Viswanathan, Shanthi, Bauer, Peter, Rolfs, Arndt, Klein, Christine
• Format: Article
• Published: ASEAN Neurological Association 2021
• Subjects: R Medicine; RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
• Online Access: http://eprints.um.edu.my/34636/
• Institution: Universiti Malaya

We describe the clinical features of two sisters with Parkinson?s disease (PD) of Indian descent living in Malaysia. Both were homozygous for the known PINK1 mutation p.Leu489Pro (c.1466T>C). The proband, who has been followed up by us over a span of 35 years, had a fairly ?classic? clinical presentation for PARK-PINK1, including young onset, a clear response to dopamine replacement therapy, and development of troublesome motor fluctuations and dyskinesias. Her dyskinesias improved substantially with clozapine treatment, which to our knowledge has not specifically been reported for PARK-PINK1; this treatment has been sustained for nearly a decade. The clinical phenotype of the older sister was more akin to later-onset ?idiopathic? PD; however, her brain MRI showed abnormal signal in the posterior limb of the internal capsules and the hypothalamus. Our report contributes to the scarce literature on monogenic PD in the Malaysian / Indian population, and further supports the pathogenicity of the PINK1 p.Leu489Pro variant.