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Case Reports
. 2024 Apr;17(2):213-217.
doi: 10.14802/jmd.24009. Epub 2024 Jan 31.

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

Shen-Yang Lim  1   2 , Ai Huey Tan  1   2 , Jia Nee Foo  3   4 , Yi Jayne Tan  5 , Elaine Gy Chew  3   4 , Azlina Ahmad Annuar  6 , Alfand Marl Dy Closas  7 , Azalea Pajo  8 , Jia Lun Lim  6 , Yi Wen Tay  6 , Anis Nadhirah  9 , Jia Wei Hor  2 , Tzi Shin Toh  2 , Lei Cheng Lit  9 , Jannah Zulkefli  2 , Su Juen Ngim  1 , Weng Khong Lim  10   11   12   13 , Huw R Morris  14 , Eng-King Tan  5 , Adeline Sl Ng  5
Affiliations
Case Reports

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

Shen-Yang Lim et al. J Mov Disord. 2024 Apr.

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.

Keywords: GBA1; Acid sphingomyelinase; Genetics; Lysosomal; Progressive supranuclear palsy; SMPD1; Sphingolipid.

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Conflict of interest statement

Conflicts of Interest

The authors have no financial conflicts of interest.

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