Loss-of-Function Variant in the SMPD1 Gene in Progressive Supranuclear Palsy-Richardson Syndrome Patients of Chinese Ancestry

Author: Shen-Yang LIM ¹ ; Ai Huey TAN ; Jia Nee FOO ; Yi Jayne TAN ; Elaine GY CHEW ; Azlina Ahmad ANNUAR ; Alfand Marl Dy CLOSAS ; Azalea PAJO ; Jia Lun LIM ; Yi Wen TAY ; Anis NADHIRAH ; Jia Wei HOR ; Tzi Shin TOH ; Lei Cheng LIT ; Jannah ZULKEFLI ; Su Juen NGIM ; Weng Khong LIM ; Huw R. MORRIS ; Eng-King TAN ; Adeline SL NG
Author Information

1. Division of Neurology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
Publication Type:3
From:Journal of Movement Disorders 2024;17(2):213-217
CountryRepublic of Korea
Language:English
Abstract: Lysosomal dysfunction plays an important role in neurodegenerative diseases, including Parkinson’s disease (PD) and possibly Parkinson-plus syndromes such as progressive supranuclear palsy (PSP). This role is exemplified by the involvement of variants in the GBA1 gene, which results in a deficiency of the lysosomal enzyme glucocerebrosidase and is the most frequently identified genetic factor underlying PD worldwide. Pathogenic variants in the SMPD1 gene are a recessive cause of Niemann–Pick disease types A and B. Here, we provide the first report on an association between a loss-of-function variant in the SMPD1 gene present in a heterozygous state (p.Pro332Arg/p.P332R, which is known to result in reduced lysosomal acid sphingomyelinase activity), with PSP-Richardson syndrome in three unrelated patients of Chinese ancestry.