RRP12 Variants Are Associated With Autosomal Recessive Brain Calcifications
Edoardo Monfrini1,2, Paola Rinchetti3, Mathieu Anheim4,5,6
1Dino Ferrari Center, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
Summary
Researchers identified RRP12 as a novel gene causing primary brain calcifications. This discovery links genetic factors to brain calcifications and associated neurological conditions like dystonia.
Area of Science:
- Genetics
- Neurology
- Molecular Biology
Background:
- Primary brain calcifications are linked to inherited diseases affecting neurovascular, mitochondrial, and nucleic acid metabolism.
- Genetic factors are implicated in various forms of primary brain calcifications.
Purpose of the Study:
- To identify a new genetic cause for primary brain calcifications in patients without a known genetic diagnosis.
- Investigate the role of the RRP12 gene in brain calcification disorders.
Main Methods:
- Exome sequencing and homozygosity mapping were used to analyze Pakistani patients.
- RRP12 variants were screened in French and Chinese patient cohorts.
- RRP12 loss-of-function was studied in patient fibroblasts and a zebrafish model.
Main Results:
- Rare homozygous and biallelic variants in RRP12 were identified in patients with brain calcifications and dystonia.
- Reduced RRP12 protein and abnormal nucleolar morphology were observed in patient cells.
- RRP12 knockdown in zebrafish led to developmental defects and lethality.
Conclusions:
- RRP12 is a newly identified candidate gene for autosomal recessive brain calcifications.
- Mutations in RRP12 may present with a broad clinical spectrum, from severe early-onset to milder adult-onset forms.
