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

Lim, Shen-Yang; Tan, Ai Huey; Foo, Jia Nee; Tan, Yi Jayne; Chew, Elaine GY; Annuar, Azlina Ahmad; Closas, Alfand Marl Dy; Pajo, Azalea; Lim, Jia Lun; Tay, Yi Wen; Nadhirah, Anis; Hor, Jia Wei; Toh, Tzi Shin; Lit, Lei Cheng; Zulkefli, Jannah; Ngim, Su Juen; Lim, Weng Khong; Morris, Huw R.; Tan, Eng-King; Ng, Adeline SL

J Mov Disord. 2024 Apr;17(2):213-217. 10.14802/jmd.24009.

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

Lim SY ^1,2
Tan AH ^1,2
Foo JN ^3,4
Tan YJ ⁵
Chew EG ^3,4
Annuar AA ⁶
Closas AMD ⁷
Pajo A ⁸
Lim JL ⁶
Tay YW ⁶
Nadhirah A ⁹
Hor JW ²
Toh TS ²
Lit LC ⁹
Zulkefli J ²
Ngim SJ ¹
Lim WK ^10,11,12,1
Morris HR ¹⁴
Tan EK ⁵
Ng AS ⁵

Affiliations

¹Division of Neurology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
²The Mah Pooi Soo & Tan Chin Nam Centre for Parkinson’s & Related Disorders, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
³Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore
⁴Laboratory of Neurogenetics, Genome Institute of Singapore, A*STAR, Singapore
⁵Department of Neurology, National Neuroscience Institute, Singapore
⁶Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
⁷Metro Davao Medical and Research Center, Health Science and Wellness Center, Davao City, Philippines
⁸Department of Clinical Epidemiology, University of the Philippines - College of Medicine, Manila, Philippines
⁹Department of Physiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
¹⁰SingHealth Duke-NUS Institute of Precision Medicine, Singapore
¹¹SingHealth Duke-NUS Genomic Medicine Centre, Singapore
¹²Cancer & Stem Cell Biology Program, Duke-NUS Medical School, Singapore
¹³Laboratory of Genome Variation Analytics, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore
¹⁴Department of Clinical and Movement Neurosciences, University College London, Institute of Neurology, London, UK

KMID: 2554696
DOI: http://doi.org/10.14802/jmd.24009

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.

Keyword

Progressive supranuclear palsy; Genetics; Lysosomal; Sphingolipid; Acid sphingomyelinase

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

Abstract

Keyword

Cited

Save citations to file

Email citations