Novel SLC20A2 mutation in a Japanese pedigree with primary familial brain calcification

Kuroi, Yasuhiro; Akagawa, Hiroyuki; Yoneyama, Taku; Kikuchi, Asami; Maegawa, Tatsuya; Kasuya, Hidetoshi

doi:10.1016/j.jns.2019.02.033

Cited by 3 publications

(3 citation statements)

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“…alignments amongst species indicated that this mutation was located at a highly conserved amino acid sequence at which mutations have increased probability to induce structural changes and Slc20 dysfunction, subsequently leading to a disturbance in the uptake of inorganic phosphorus in cells (38). Mutations in Slc20a2 have been increasingly reported in primary familial brain calcification cases (39,40) and, to the best of our knowledge, the present study is the first to report Slc20a2 mutation in patients with HMe. Sekine et al (38) reported that Slc20a2 variants significantly decreased inorganic phosphate transport activity in endothelial cells induced from induced pluripotent stem cells (iPS-cs) derived from patients with idiopathic basal ganglia calcification patients compared with control iPS-ecs.…”

Section: Discussionsupporting

confidence: 58%

Whole‑exome sequencing identifies a novel mutation of SLC20A2 (c.C1849T) as a possible cause of hereditary multiple exostoses in a Chinese family

Lin

Zhu

et al. 2020

Mol Med Rep

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although the main causative genes for hereditary multiple exostoses (HMe) are exostosin (EXT)-1 and EXT-2, there are numerous patients with HMe without EXT-1 and EXT-2 mutations. The present study aimed to identify novel candidate genes for the development of HMe in patients without EXT-1 and EXT-2 mutations. Whole-exome sequencing was performed in a chinese family with HMe and without EXT-1 and EXT-2 mutations, followed by a combined bioinformatics pipeline including annotation and filtering processes to identify candidate variants. candidate variants were then validated using Sanger sequencing. a total of 1,830 original variants were revealed to be heterozygous mutations in three patients with HMe which were not present in healthy controls. Two mutations [c.c1849T in solute carrier family 20 member 2 (Slc20a2) and c.G506a in leucine zipper and eF-hand containing transmembrane protein 1 (leTM1)] were identified as possible causative variants for HME through a bioinformatics filtering procedure and harmful prediction. Sanger sequencing results confirmed these two mutations in all patients with HME. A mutation in Slc20a2 (c.c1849T) led to a change in an amino acid (p.r617c), which may be involved in the development of HMe by inducing metabolic disorders of phosphate and abnormal proliferation and differentiation in chondrocytes. in conclusion, the present study revealed two mutations [Slc20a2 (c.c1849T) and leTM1 (c.G506a) in a chinese family with HMe. The mutation in Slc20a2 (c.c1849T)] was more likely to be involved in the development of HMe.

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Section: Discussionsupporting

confidence: 58%

Whole‑exome sequencing identifies a novel mutation of SLC20A2 (c.C1849T) as a possible cause of hereditary multiple exostoses in a Chinese family

Lin

Zhu

et al. 2020

Mol Med Rep

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“…In the present study, mutations in SLC20A2 (c.C1849T) led to a change in amino acid (p.R617C), which might induce structural changes and dysfunction of Pit-2, leading to disturbance of phosphate homeostasis in cells. Mutations in SLC20A2 have been reported to be a major cause of primary familial brain calcification (Lemos et al 2015;Kuroi et al 2019). However, the proband in our study did not have brain calcification (Figure 5).…”

Section: Discussioncontrasting

confidence: 49%

Whole-exome sequencing identified a novel mutation of SLC20A2 (c.C1849T) in a Chinese family with hereditary multiple exostoses

Lin

Zhu

et al. 2020

Preprint

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Background: Although the main causative genes for hereditary multiple exostoses (HME) are EXT-1 and EXT-2, there are still many HME patients without EXT-1 and EXT-2 mutations. This study aimed to identify novel candidate genes for the development of HME in patients without EXT-1 and EXT-2 mutations.Methods: Whole-exome sequencing was performed in a typical Chinese HME family without EXT-1 and EXT-2 mutations, followed by a combined bioinformatics pipeline including annotation and filtering process to identify candidate variants. Candidate variants were then validated by Sanger sequencing.Results: A total of 1830 original variants were revealed to be heterozygous mutations in the three patients suffering from HME that were not present in the healthy controls. Two mutations (c.C1849T in SLC20A2 and c.G506A in LETM1) were identified as a possible causative variant for HME through a bioinformatics filtering procedure and harmful prediction. Sanger sequencing results confirmed these two mutations in all patients with HME. A mutation in SLC20A2 (c.C1849T) led to a change in amino acid (p.R617C), which may be involved in the development of HME by inducing metabolic disorders of phosphate and abnormal proliferation and differentiation in chondrocytes.Conclusions: The present study revealed two mutations [SLC20A2 (c.C1849T) and LETM1 (c.G506A) in a Chinese HME family. The mutation in SLC20A2 (c.C1849T) is more likely to be involved in the development of HME.

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“…Of note, pontine calcifications are typically overserved in subjects with mutations or MYORG [62]. In subjects with PFBC, serum levels of calcium, parathormone (PRH), and vitamin D were found to be within range [26,41,42,50,51,55,57,[63][64][65][66][67].…”

Section: Primary Familial Brain Calcifications: Clinical Aspectsmentioning

confidence: 99%

Brain Calcifications: Genetic, Molecular, and Clinical Aspects

Monfrini

Arienti

Rinchetti

et al. 2023

IJMS

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Many conditions can present with accumulation of calcium in the brain and manifest with a variety of neurological symptoms. Brain calcifications can be primary (idiopathic or genetic) or secondary to various pathological conditions (e.g., calcium–phosphate metabolism derangement, autoimmune disorders and infections, among others). A set of causative genes associated with primary familial brain calcification (PFBC) has now been identified, and include genes such as SLC20A2, PDGFB, PDGFRB, XPR1, MYORG, and JAM2. However, many more genes are known to be linked with complex syndromes characterized by brain calcifications and additional neurologic and systemic manifestations. Of note, many of these genes encode for proteins involved in cerebrovascular and blood–brain barrier functions, which both represent key anatomical structures related to these pathological phenomena. As a growing number of genes associated with brain calcifications is identified, pathways involved in these conditions are beginning to be understood. Our comprehensive review of the genetic, molecular, and clinical aspects of brain calcifications offers a framework for clinicians and researchers in the field.

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Novel SLC20A2 mutation in a Japanese pedigree with primary familial brain calcification

Cited by 3 publications

References 13 publications

Whole‑exome sequencing identifies a novel mutation of SLC20A2 (c.C1849T) as a possible cause of hereditary multiple exostoses in a Chinese family

Whole‑exome sequencing identifies a novel mutation of SLC20A2 (c.C1849T) as a possible cause of hereditary multiple exostoses in a Chinese family

Whole-exome sequencing identified a novel mutation of SLC20A2 (c.C1849T) in a Chinese family with hereditary multiple exostoses

Brain Calcifications: Genetic, Molecular, and Clinical Aspects

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