A Gain-of-Function Variant in Dopamine D2 Receptor and Progressive Chorea and Dystonia Phenotype.

Background: We describe a 4-generation Dutch pedigree with a unique dominantly inherited clinical phenotype of a combined progressive chorea and cervical dystonia carrying a novel heterozygous dopamine D2 receptor (DRD2) variant.

Objectives: The objective of this study was to identify the genetic cause of the disease and to further investigate the functional consequences of the genetic variant.

Methods: After detailed clinical and neurological examination, whole-exome sequencing was performed.

Cortical pencil lining on SWI MRI in NBIA and healthy aging.

Background: Neurodegeneration with brain iron accumulation (NBIA) is characterized by pathological iron accumulation in the subcortical nuclei and the cortex. As age-related iron accumulation studies in these structures are lacking in healthy aging, we aimed to characterize the dynamics of age-dependent iron accumulation in subcortical nuclei in healthy aging and selected NBIA cases. This is fundamental to understand the natural age-related iron deposition in the healthy brain prior to using this marker as a potential prognostic or diagnostic tool in neurodegenerative disorders.

Autosomal dominant mitochondrial membrane protein-associated neurodegeneration (MPAN).

Background: Mitochondrial membrane protein-associated neurodegeneration (MPAN) is caused by pathogenic sequence variants in C19orf12. Autosomal recessive inheritance has been demonstrated. We present evidence of autosomal dominant MPAN and propose a mechanism to explain these cases.