Dataset Information

Brain hypoperfusion and nigrostriatal dopaminergic dysfunction in primary familial brain calcification caused by novel MYORG variants: case report.

ABSTRACT: BACKGROUND:Primary familial brain calcification (PFBC) is a rare inherited disease characterized by multiple calcified foci in the brain parenchyma. MYORG is the first gene found to be associated with autosomal recessive PFBC. The precise pathogenic mechanism of neurodegeneration in PFBC remains unclear. The clinical phenotypes of PFBC are variable, and there is no clear correlation between clinical manifestations and radiological and pathological features of calcification. CASE PRESENTATION:Two sisters in a Taiwanese family presented with young-onset Parkinsonism and multifocal dystonia. Their brain CTs showed multiple intracerebral calcifications. The genetic study detected two heterozygous novel variants, c.104?T?>?A (p.Met35Lys) and c.850?T?>?C (p.Cys284Arg) in the MYORG gene. In both patients, MR susceptibility weighted images revealed calcification of the deep medullary veins. Tc99m ECD SPECT demonstrated a significant decrease of tracer uptake in the brain cortex and subcortical gray matter. Tc99m TRODAT-1 SPECT revealed decreased tracer uptake in the bilateral striatum. CONCLUSION:Two novel MYORG variants were identified in Taiwanese family members presenting with PFBC. Abnormalities in the brain perfusion and dopamine transporter SPECTs suggest that cerebral ischemia due to extensive calcified vasculopathy, disruption of the basal ganglia-thalamo-cortical circuit, and nigrostriatal dopaminergic dysfunction are plausible pathogenic mechanisms of neurodegeneration in PFBC patients. Further investigation into the correlations between the pathogenicity-implicated imaging findings and the clinical phenotype are recommended.

SUBMITTER: Chen SY

PROVIDER: S-EPMC7460774 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Brain hypoperfusion and nigrostriatal dopaminergic dysfunction in primary familial brain calcification caused by novel MYORG variants: case report.

Chen Shih-Ying SY Lin Wei-Che WC Chang Yung-Yee YY Lin Tsu-Kung TK Lan Min-Yu MY

BMC neurology 20200901 1

<h4>Background</h4>Primary familial brain calcification (PFBC) is a rare inherited disease characterized by multiple calcified foci in the brain parenchyma. MYORG is the first gene found to be associated with autosomal recessive PFBC. The precise pathogenic mechanism of neurodegeneration in PFBC remains unclear. The clinical phenotypes of PFBC are variable, and there is no clear correlation between clinical manifestations and radiological and pathological features of calcification.<h4>Case prese ...[more]

PMID: 32873236

Similar Datasets

Project description:Primary familial brain calcification (PFBC) is a genetic neurological disorder characterized by symmetric brain calcifications that manifest with variable neurological symptoms. This study aimed to explore the genetic basis of PFBC and elucidate the underlying pathophysiological mechanisms. Six patients from four pedigrees with brain calcification were enrolled. Whole-exome sequencing identified two novel homozygous variants, c.488G > T (p.W163L) and c.2135G > A (p.W712*), within the myogenesis regulating glycosidase (MYORG) gene. Cerebellar ataxia (n = 5) and pyramidal signs (n = 4) were predominant symptoms, with significant clinical heterogeneity noted even within the same family. An autopsy of one patient revealed extensive brainstem calcifications, sparing the cerebral cortex, and marked by calcifications predominantly in capillaries and arterioles. The pathological study suggested morphological alterations characterized by shortened foot processes within astrocytes in regions with pronounced calcification and decreased immunoreactivity of AQP4. The morphology of astrocytes in regions without calcification remains preserved. Neuronal loss and gliosis were observed in the basal ganglia, thalamus, brainstem, cerebellum, and dentate nucleus. Notably, olivary hypertrophy, a previously undescribed feature in MYORG-PFBC, was discovered. Neuroimaging showed reduced blood flow in the cerebellum, highlighting the extent of cerebellar involvement. Among perivascular cells constituting the blood-brain barrier (BBB) and neurovascular unit, MYORG is most highly expressed in astrocytes. Astrocytes are integral components of the BBB, and their dysfunction can precipitate BBB disruption, potentially leading to brain calcification and subsequent neuronal loss. This study presents two novel homozygous variants in the MYORG gene and highlights the pivotal role of astrocytes in the development of brain calcifications, providing insights into the pathophysiological mechanisms underlying PFBC associated with MYORG variants.

Project description:Rapid eye movement sleep behavior disorder is parasomnia characterized by symptoms of dream enactment and loss of muscle atonia during rapid eye movement sleep. Mild motor impairment is present in some patients with rapid eye movement sleep behavior disorder and presumed to be a risk factor for conversion to synucleinopathies. The purpose of this study is to identify patients with mild motor impairment by evaluating finger tapping and to investigate its pathophysiology. Twenty-three patients with rapid eye movement sleep behavior disorder and 20 healthy control subjects were recruited in the present study. We accurately evaluated finger tapping including amplitude, peak open, and close speed with a magnetic sensing device and identified patients with mild motor impairment. Moreover, we performed 123I-2β-carbomethoxy-3β-(4-iodophenyl) nortropane SPECT and resting state functional MRI. 123I-2β-carbomethoxy-3β-(4-iodophenyl) nortropane uptake for each bilateral caudate, anterior putamen, and posterior putamen was calculated and the resting state functional connectivity of sensorimotor network was analyzed. Using finger tapping parameters, we identified eight patients with mild motor impairment. In patients with mild motor impairment, all finger tapping parameters were significantly impaired when compared to patients with normal motor function, while they exhibited no significant differences in Unified Parkinson's Disease Rating Scale part III score. 123I-2β-carbomethoxy-3β-(4-iodophenyl) nortropane uptake in the right posterior putamen, bilateral anterior putamen, and caudate was significantly lower when compared to healthy controls or patients with rapid eye movement sleep behavior disorder with normal motor function. These patients also exhibited decreased cortico-striatal functional connectivity and increased cortico-cerebellar functional connectivity when compared to healthy controls or patients with normal motor function. Our results show that mild motor impairment in rapid eye movement sleep behavior disorder evaluated by finger tapping task presented mild nigrostriatal dopaminergic dysfunction as well as alterations in resting state sensorimotor network. Although longitudinal follow up is necessary, such patients may have higher risk of short-term conversion to synucleinopathies.

Dataset Information

Brain hypoperfusion and nigrostriatal dopaminergic dysfunction in primary familial brain calcification caused by novel MYORG variants: case report.

Publications

Brain hypoperfusion and nigrostriatal dopaminergic dysfunction in primary familial brain calcification caused by novel MYORG variants: case report.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets