TY - JOUR
T1 - PINK1 p.Leu347Pro mutations in Malays: Prevalence and illustrative cases
AU - Tan, Ai Huey
AU - Lohmann, Katja
AU - Tay, Yi Wen
AU - Lim, Jia Lun
AU - Ahmad-Annuar, Azlina
AU - Ramli, Norlisah
AU - Chin, Yen Theng
AU - Mawardi, Ahmad Shahir
AU - Azmi, Khairul
AU - Aziz, Zariah Abdul
AU - Puvanarajah, Santhi Datuk
AU - Bauer, Peter
AU - Klein, Christine
AU - Rolfs, Arndt
AU - Lim, Shen Yang
PY - 2020/10
Y1 - 2020/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85089804451&partnerID=8YFLogxK
U2 - 10.1016/j.parkreldis.2020.08.015
DO - 10.1016/j.parkreldis.2020.08.015
M3 - Journal articles
C2 - 32861104
AN - SCOPUS:85089804451
SN - 1353-8020
VL - 79
SP - 34
EP - 39
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
ER -