Objective: We present the clinical and mutational spectrum of SLC20A2, PDGFB, PDGFRB, XPR1, and MYORG mutations, thereby adding a new gene, MYORG, recently found to be mutated in patients with primary familial brain calcification (PFBC) to MDSGene.

Background: The MDSGene database (www.mdsgene.org) summarizes genetic and phenotypic information on >500 mutations found in >1000 patients with various movement disorders reported in the literature.

Method: A systematic literature screen for SLC20A2, PDGFB, PDGFRB, XPR1, and MYORG in PubMed identified 51 articles that reported at least one mutation-positive individual with PFBC and provided clinical information on mutation carriers. Mutations were included if they had a minor allele frequency <1% (based on the ExAC Browser, dbSNP or unaffected control individuals screened in the publication). We extracted radiological data and 70 other phenotypic features for 367 clinically affected and unaffected mutation carriers.

Results: A total of 367 mutation-positive, symptomatic or asymptomatic individuals with PFBC were included in our review. Sixty-five patients from 14 families carried MYORG mutations. General motor signs were the most frequently reported clinical feature in 165 individuals (43.8%) including parkinsonism (18.3%) and speech disturbance (14.1%). A considerable proportion of patients also displayed non-motor signs, such as cognitive deficits (24.1%) or headache (15.4%). At 30.5 years, PDGFB mutation carriers had the lowest median disease age of onset (AOO). A total of 124 mutation carriers were described as clinically asymptomatic (32.9%). Detailed cranial computed tomography (CCT) data was available for 320 patients (84.9%), showing that brain calcification was most common in the basal ganglia (77.2%). Overall, there was a large percentage of missing (unspecified) clinical and neuroradiological data.

Conclusion: Mutations in one of the five genes known genes to cause PFBC lead to calcification of mostly the basal ganglia with high phenotypic variability within the same and across genes and with reduced penetrance of clinical signs in about a third of the mutation carriers. Our review complements the PFBC section of MDSGene by adding MYORG that was recently identified and, as for previous entries, identifies significant data gaps in the present literature, especially for non-motor symptoms.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/reviewing-the-clinical-and-mutational-spectrum-of-slc20a2-pdgfb-pdgfrb-xpr1-and-myorg-mutations-in-primary-familial-brain-calcification-pfbc-for-mdsgene/