A novel ATP13A2 variant causing complicated hereditary spastic paraplegia.
Neurol Sci
; 45(4): 1749-1753, 2024 Apr.
Article
in En
| MEDLINE
| ID: mdl-38252374
ABSTRACT
BACKGROUND:
ATP13A2 is a monogenic causative gene of Parkinson's disease, whose biallelic mutations can result in Kufor-Rakeb syndrome. Biallelic mutations in ATP13A2 have also been reported in pure or complicated hereditary spastic paraplegia (HSP). Here, we report clinical, neuroimaging, and genetic findings from a patient with a novel homozygous mutation in ATP13A2 presenting with HSP plus parkinsonism.METHODS:
Whole genome sequencing was performed on the patient, a 46-year-old Chinese woman from a consanguineous family, to identify the genetic cause. Furthermore, functional studies of the identified ATP13A2 mutation were conducted.RESULTS:
The patient initially presented with abnormal gait because of lower-limb spasticity and recurrent seizures. Parkinsonism (presenting as bradykinesia and rigidity) and peripheral neuropathy in lower limbs further evolved and resulted in her eventual use of a wheelchair. Symmetrically decreased dopamine transporter density was detected within the bilateral putamen and caudate nucleus in dopamine transporter-positron emission tomography. Genetic analysis revealed a novel homozygous missense mutation in ATP13A2 (c.2780 T > C, p.Leu927Pro), which was heterozygous in the patient's parents and son. Functional studies suggested that this mutation results in the reduced expression and altered subcellular localization of ATP13A2.CONCLUSIONS:
Our report broadens the genetic and phenotypic spectrum of ATP13A2-related HSP. Further research is needed to fully elucidate the mechanism linking ATP13A2 variants to HSP.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Parkinson Disease
/
Spastic Paraplegia, Hereditary
/
Parkinsonian Disorders
Type of study:
Prognostic_studies
Limits:
Female
/
Humans
/
Middle aged
Language:
En
Journal:
Neurol Sci
Journal subject:
NEUROLOGIA
Year:
2024
Type:
Article
Affiliation country:
China