A heterozygous deletion of PDGFB gene causes paroxysmal kinesigenic dyskinesia with primary familial brain calcification

Duan, Ruonan; Zhao, Dandan; Liu, Yiming; Yan, Chuanzhu

doi:10.1016/j.parkreldis.2021.10.021

Cited by 2 publications

(1 citation statement)

References 18 publications

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“…These variants are predicted to introduce a translation termination (stop) codon at amino acid residues 140 respectively 191 and are absent in gnomAD v2.1 (https://gnomad.broadinstitute.org/). Other truncating PDGFB variants had previously been described as causes of PFBC [9,[21][22][23][24][25], and for this reason both novel variants have been classified as likely to be pathogenic according to the American College of Medical Genetics [26]. The sequenced data was also filtered by using a stroke gene panel for all genes reported to potentially cause monogenic stroke, including stroke related to cerebral small vessel disease [27,28].…”

Section: Genetic Analysesmentioning

confidence: 99%

Small vessel disease in primary familial brain calcification with novel truncating PDGFB variants

Yektay Farahmand,

Wasselius,

Englund

et al. 2024

Neurol Neurochir Pol.

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Introduction. Primary familial brain calcification (PFBC) is a neurodegenerative disease characterised by bilateral calcification in the brain, especially in the basal ganglia, leading to neurological and neuropsychiatric manifestations. White matter hyperintensities (WMH) have been described in patients with PFBC and pathogenic variants in the gene for platelet-derived growth factor beta polypeptide (PDGFB), suggesting a manifest cerebrovascular process. We present below the cases of two PFBC families with PDGFB variants and stroke or transient ischaemic attack (TIA) episodes. We examine the possible correlation between PFBC and vascular events as stroke/TIA, and evaluate whether signs for vascular disease in this condition are systemic or limited to the cerebral vessels.Material and methods. Two Swedish families with novel truncating PDGFB variants, p.Gln140* and p.Arg191*, are described clinically and radiologically. Subcutaneous capillary vessels in affected and unaffected family members were examined by light and electron microscopy.Results. All mutation carriers showed WMH and bilateral brain calcifications. The clinical presentations differed, with movement disorder symptoms dominating in family A, and psychiatric symptoms in family B. However, affected members of both families had stroke, TIA, and/or asymptomatic intracerebral ischaemic lesions. Only one of the patients had classical vascular risk factors. Skin microvasculature was normal.Conclusions. Patients with these PDGFB variants develop microvascular changes in the brain, but not the skin. PDGFB-related small vessel disease can manifest radiologically as cerebral haemorrhage or ischaemia, and may explain TIA or stroke in patients without other vascular risk factors.

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Section: Genetic Analysesmentioning

confidence: 99%

Small vessel disease in primary familial brain calcification with novel truncating PDGFB variants

Yektay Farahmand,

Wasselius,

Englund

et al. 2024

Neurol Neurochir Pol.

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The Pathology of Primary Familial Brain Calcification: Implications for Treatment

Sun

Luo

et al. 2022

Neurosci. Bull.

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Primary familial brain calcification (PFBC) is an inherited neurodegenerative disorder mainly characterized by progressive calcium deposition bilaterally in the brain, accompanied by various symptoms, such as dystonia, ataxia, parkinsonism, dementia, depression, headaches, and epilepsy. Currently, the etiology of PFBC is largely unknown, and no specific prevention or treatment is available. During the past 10 years, six causative genes (SLC20A2, PDGFRB, PDGFB, XPR1, MYORG, and JAM2) have been identified in PFBC. In this review, considering mechanistic studies of these genes at the cellular level and in animals, we summarize the pathogenesis and potential preventive and therapeutic strategies for PFBC patients. Our systematic analysis suggests a classification for PFBC genetic etiology based on several characteristics, provides a summary of the known composition of brain calcification, and identifies some potential therapeutic targets for PFBC.

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A heterozygous deletion of PDGFB gene causes paroxysmal kinesigenic dyskinesia with primary familial brain calcification

Cited by 2 publications

References 18 publications

Small vessel disease in primary familial brain calcification with novel truncating PDGFB variants

Small vessel disease in primary familial brain calcification with novel truncating PDGFB variants

The Pathology of Primary Familial Brain Calcification: Implications for Treatment

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