# A Novel Frameshift Mutation in SLC20A2 in a Korean Patient with Primary Brain Calcification, Parkinsonism and Memory Impairment

## TL;DR

A new mutation in the SLC20A2 gene is linked to brain calcification and neurological symptoms in a Korean patient.

## Contribution

A novel frameshift mutation in SLC20A2 is identified as a cause of primary brain calcification.

## Key findings

- A c.1152_1153delCA frameshift mutation in SLC20A2 was found in a patient with brain calcification and neurological symptoms.
- Reduced SLC20A2 protein levels in plasma suggest a loss-of-function mechanism due to the mutation.
- The patient showed increased amyloid-beta oligomerization, hinting at a potential link between SLC20A2 and amyloid pathways.

## Abstract

Objectives: The patient presented various neurological symptoms in her 50s, such as memory issues, insomnia, depression, and motor impairment. Diverse investigations were performed to identify the underlying causes on her neurological symptoms and understand her neuro- deteriorations. Methods: Clinical neurological and brain imaging analyses: CT, MRI and PET were performed on the patient. Blood was drawn for the whole-exome sequencing and functional studies with biomarker for amyloid-beta oligomers and SLC20A2 protein in plasma. Results: Brain imaging revealed calcifications in multiple regions, including the subcortical white matter, basal ganglia, thalami, and dentate nuclei. Genetic analysis revealed a c.1152_1153delCA, p.Asn384Lysfs*30 variant in SLC20A2 gene. The decreased SLC20A2 protein levels in plasma in comparison to healthy controls suggested a loss-of-function mechanism from the mutation. The patient had a positive AlzOn result, indicating an increased tendency for amyloid oligomerization and suggesting a potential indirect link between SLC20A2 and amyloid-beta pathways. Conclusions: A novel frameshift mutation, Asn384Lysfs*30, in the SLC20A2 gene was identified in a patient with Primary Brain Calcification (PBC). This mutation was located in a critical large loop region of the protein, where other similar mutations (e.g., Gly366fs89, Ser385Ilefs*70) were previously reported. These findings indicated that mutations in SLC20A2 caused the reduced protein expressions, potentially resulting PBC through haploinsufficiency.