- VPS13C is a protein-coding gene involved in the regulation of mitochondrial function through the endolysosomal pathway in neurons. Homozygous and compound heterozygous VPS13C mutations are etiologically associated with early-onset Parkinson’s disease (PD). Moreover, recent studies linked biallelic VPS13C mutations with the development of dementia with Lewy bodies (DLB). Neuropathological studies on two mutated subjects showed diffuse Lewy body disease. In this article, we report the clinical and genetic findings of two subjects affected by early-onset PD carrying three novel VPS13C mutations (i.e., one homozygous and one compound heterozygous), and review the previous literature on the genetic and clinical findings of VPS13C-mutated patients, contributing to the knowledge of this rare genetic alpha-synucleinopathy.
- To perform the genetic characterization of a cohort with familial parkinsonism and cognitive-behavioral syndrome.
- Homozygous sequestomosome-1 gene mutations have been recently linked to neurodegeneration with dystonia, ataxia and gaze palsy. Seven affected families were identified thus far.
- Early Onset Parkinson's Disease (EOPD) is genetically heterogeneous. PARK2 mutations are the commonest cause of autosomal recessive EOPD followed by PINK1.DJ1 mutations is rare and there is scarce literature on its phenotype and long term outcome.
- The 18p- syndrome is a chromosomal disorder caused by the deletion of all or part of the short arm of chromosome 18 (18p) . Clinical manifestations include post-natal growth retardation, short stature, mental retardation and dysmorphic features. Dystonia affects some 18p- patients, possibly related to the extent of the deletion; its frequency is probably underestimated given that in cases with severe neurological and skeletal malformations, dystonia may be overlooked. Only a subset of patients develop autoimmune disorders.
- Corticobasal degeneration (CBD) is a neurodegenerative, sporadic disorder of unknown cause. Few familial cases have been described.
- The genetic cause of late-onset focal and segmental dystonia remains unknown in most individuals. Recently, mutations in Thanatos-associated protein domain containing, apoptosis associated protein 1 (THAP1) have been described in DYT6 dystonia and associated with some cases of familial and sporadic late-onset dystonia in Caucasians. We are not aware of any previous descriptions of familial dystonia in African–Americans or reports of THAP1 mutations in African–Americans. Herein, we characterize an African–American (AA) kindred with late-onset primary dystonia, clinically and genetically.