PINK1 p.Leu347Pro mutations in Malays: Prevalence and illustrative cases. (October 2020)

• Record Type: Journal Article
• Authors: Tan, Ai Huey; Lohmann, Katja; Tay, Yi Wen; Lim, Jia Lun; Ahmad-Annuar, Azlina; Ramli, Norlisah; Chin, Yen Theng; Mawardi, Ahmad Shahir; Azmi, Khairul; Aziz, Zariah Abdul; Puvanarajah, Santhi Datuk; Bauer, Peter; Klein, Christine; Rolfs, Arndt; Lim, Shen-Yang
• Is Part Of: Parkinsonism & related disorders. Volume 79(2020)
• Page Start: 34
• Page End: 39
• Publication Date: 2020-10
• Subjects: Parkinson's disease -- Autosomal recessive early-onset Parkinson's disease -- PINK1 -- Genetics -- Asian -- Corticospinal tract -- Swallow tail sign; Parkinson's disease -- Periodicals; Movement disorders -- Periodicals; Movement Disorders -- Periodicals; Nerve Degeneration -- Periodicals; Nervous System Diseases -- Periodicals; Parkinson Disease -- Periodicals; Tremor -- Periodicals; Parkinson, Maladie de -- Périodiques; Parkinson's disease; 616.833
• DOI: 10.1016/j.parkreldis.2020.08.015
• Languages: English
• ISSNs: 1353-8020

Abstract

Abstract: Background: An improved understanding of the genetic determinants of Parkinson's disease (PD) in underrepresented populations, and better characterization of genotype-phenotype correlations in monogenic PD, are needed. Scarce literature exists regarding the genetic aetiology of PD in Malays, who comprise 200 million individuals in South-East Asia. Phenotypic data regarding PARK- PINK1 are also limited. Methods: A multi-ethnic cohort of PD patients from Malaysia ( n = 499, including 185 Malays) were tested using a next-generation sequencing-based PD gene panel. The prevalence and clinico-radiological features of patients with the PINK1 p. Leu347Pro mutation are described. This mutation has previously only been reported in people of Filipino or Chamorro (native Guamanian) ancestry. Results: Homozygous p. Leu347Pro mutations were found in five unrelated Malay patients, yielding a prevalence of 6.9% among Malays with PD onset ≤50 years (2.7% of the Malay group overall). This variant was not detected in the homozygous state in 300 Malay controls, but two were heterozygous carriers (0.67%) indicating a relatively high population frequency in keeping with the high frequency of PARK- PINK1 among Malay patients. Interesting clinical features were observed, e.g., differences in the age at PD onset and clinical progression, despite having the same point mutations. Previously unreported brain MRI abnormalities involving the corticospinal tract and hypothalamus, and "loss of the swallow tail" sign, were documented. Conclusions: This report contributes to the very limited literature on PD genetics in the Malay population, and more broadly to the epidemiological, phenotypic and neuroimaging characterization of PARK- PINK1 . It also further supports the pathogenicity of the p. Leu347Pro variant. Highlights: PARK- PINK1 is a relatively common form of monogenic PD in the Asia-Pacific. PINK1 p. Leu347Pro was previously thought to be restricted to Filipinos. We found PINK1 p. Leu347Pro to be a common cause of early-onset PD in Malays. Patients with the same mutation may have quite varied clinical phenotype. Some patients have MRI abnormalities in the corticospinal tract and hypothalamus.