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Case Reports
. 2021 Mar;22(1):65-70.
doi: 10.1007/s10048-021-00634-9. Epub 2021 Jan 20.

Expanding the genetic spectrum of primary familial brain calcification due to SLC2OA2 mutations: a case series

Luca Magistrelli  1   2 , Roberta Croce  3 , Fabiola De Marchi  1   4 , Chiara Basagni  3 , Miryam Carecchio  5 , Nicola Nasuelli  6 , Roberto Cantello  1 , Federica Invernizzi  7 , Barbara Garavaglia  7 , Cristoforo Comi  1 , Letizia Mazzini  4 , Sandra D'Alfonso #  3 , Lucia Corrado #  8
Affiliations
Case Reports

Expanding the genetic spectrum of primary familial brain calcification due to SLC2OA2 mutations: a case series

Luca Magistrelli et al. Neurogenetics. 2021 Mar.

Abstract

Primary familial brain calcification (PFBC) is a neurological condition characterized by the presence of intracranial calcifications, mainly involving basal ganglia, thalamus, and dentate nuclei. So far, six genes have been linked to this condition: SLC20A2, PDGFRB, PDGFB, and XPR1 inherited as autosomal-dominant trait, while MYORG and JAM2 present a recessive pattern of inheritance. Patients mainly present with movement disorders, psychiatric disturbances, and cognitive decline or are completely asymptomatic and calcifications may represent an occasional finding. Here we present three variants in SLC20A2, two exonic and one intronic, which we found in patients with PFBC associated to three different clinical phenotypes. One variant is novel and two were already described as variants of uncertain significance. We confirm the pathogenicity of these three variants and suggest a broadening of the phenotypic spectrum associated with mutations in SLC20A2.

Keywords: Motor neuron; Primary familil brain calcification; SLC20A2.

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Conflict of interest statement

The authors declare that they have no conflict of interest

Figures

Fig. 1
Fig. 1
a Cerebral CT scans showing the localization of the brain calcifications in the described cases. b RT-PCR analysis on 2% agarose gel electrophoresis performed using RNA derived from PBMCs of the c.290-8 A>G mutation carriers (#1a, #1b) and healthy controls and schematic representation of the alternative splicing mechanisms involving SLC20A2 (exons 2–4). The lines indicate the three different transcripts detected in the analyzed samples. c RT-PCR analysis on 2% agarose gel electrophoresis performed using RNA from PBMCs patients with c.290-8 A>G (#I.1, #I.2) and healthy controls using primers to amplify specifically the intron 2 retained isoform (transcript 3). The position of the new acceptor site and the primers used to amplify the aberrant isoform are graphically indicated. d Electropherogram relative to transcript 2 isoform showing exon 3 skipping. e Electropherogram relative to exon 5 of SLC20A2 of the case #2 showing the c.541C>T p.R181W (NM_001257180) heterozygous missense mutation. f Electropherogram relative to exon 6 of SLC20A2 gene in case #3 showing the c.687dupT p.V230Cfs*28 (NM_001257180) heterozygous mutation
See this image and copyright information in PMC

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