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Clin Genet. 2019 Mar 19. doi: 10.1111/cge.13540. [Epub ahead of print]

Identification of SLC20A2 deletions in patients with primary familial brain calcification.

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Department of Neurology and Institute of Neurology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
Fujian Key Laboratory of Molecular Neurology, Fuzhou, China.


Primary familial brain calcification (PFBC) is a rare neurological disorder. Mutations in five genes (SLC20A2, PDGFB, PDGFRB, XPR1 and MYORG) have been linked to PFBC. Here, we used SYBR green-based real-time quantitative PCR assay and denaturing high performance liquid chromatography analysis to detect copy number variants (CNVs) in 20 unrelated patients with PFBC, negatively sequenced for the five known genes. We identified three deletions in SLC20A2, including a large de novo full gene deletion and two exonic deletions confined to exon 2 and exon 6, respectively. Subsequent linked-read whole-genome sequencing of the patient with the large deletion revealed a 1.7 Mb heterozygous deletion which removed the entire coding regions of SLC20A2 as well as 21 other genes. In the family with deletion of exon 6, a missense variant of uncertain significance (SLC20A2: p.E267Q) also co-segregated with the disease. Functional assay showed the deletion could result in significantly impaired phosphate transport, whereas the p.E267Q variant did not. Our results confirm that deletion in SLC20A2 is a causal mechanism for PFBC and highlight the importance of functional study for classifying a rare missense variant as (likely) pathogenic.


PFBC; SLC20A2; deletion; functional assay; primary familial brain calcification


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