一个导致 SLC20A2 基因外显子 6 跳跃的剪接位点突变存在于一个原发性家族性脑钙化家系中。

A splice site mutation causing exon 6 skipping in SLC20A2 gene in a primary familial brain calcification family.

机构信息

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, PR China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410008, Hunan, PR China; Department of Neurology, the Brain Hospital of Hunan Province, Changsha 410008, Hunan, PR China.

出版信息

Brain Res Bull. 2019 Aug;150:261-265. doi: 10.1016/j.brainresbull.2019.01.006. Epub 2019 Jan 8.

DOI:10.1016/j.brainresbull.2019.01.006

PMID:30634018

Abstract

BACKGROUND

Primary familial brain calcification (PFBC) is a rare degenerative disease characterized by symmetrical bilateral calcinosis in the basal ganglia and other brain regions. It has an autosomal dominant inheritance pattern in most cases and exhibits genetic heterogeneity. Previous studies reported that SLC20A2, PDGFRB, PDGFB, XPR1 and MYORG are associated with PFBC, with SLC20A2 the main culprit. However, other mutations may also cause PFBC. Here, we performed a study to reveal the contributing mutations that gave rise to PFBC in a Chinese PFBC family.

METHODS

We recruited a PFBC family consisting of eight patients and eight healthy family members across three generations. Whole-exome sequencing, Sanger sequencing and RT-PCR were used to detect the genetic mutations.

RESULTS

Whole-exome sequencing revealed that c.730 + 1G > A of SLC20A2 was the candidate pathogenic mutation for the proband in this family. Genomic DNA PCR amplification and Sanger sequencing confirmed that all the patients from the family carried this mutation, while the healthy subjects in the family did not. Complementary DNA (cDNA) PCR amplification and Sanger sequencing confirmed that the patients had a mutation that caused exon 6 skipping in SLC20A2.

CONCLUSION

We identified a SLC20A2 splicing variant (c.730 + 1G > A) in a PFBC family. This mutation led to an alternative splicing event that skipped exon 6 in SLC20A2.

摘要

背景

原发性家族性脑钙化（PFBC）是一种罕见的退行性疾病，其特征是基底节和其他脑区的双侧对称钙化。在大多数情况下，它具有常染色体显性遗传模式，并表现出遗传异质性。先前的研究报道 SLC20A2、PDGFRB、PDGFB、XPR1 和 MYORG 与 PFBC 相关，其中 SLC20A2 是主要罪魁祸首。然而，其他突变也可能导致 PFBC。在这里，我们进行了一项研究，以揭示导致一个中国 PFBC 家族 PFBC 的致病突变。

方法

我们招募了一个由三代 8 名患者和 8 名健康家庭成员组成的 PFBC 家族。全外显子组测序、Sanger 测序和 RT-PCR 用于检测遗传突变。

结果

全外显子组测序显示，SLC20A2 的 c.730 + 1G > A 是该家系先证者的候选致病性突变。基因组 DNA PCR 扩增和 Sanger 测序证实，该家系所有患者均携带该突变，而家系中的健康个体则没有。cDNA PCR 扩增和 Sanger 测序证实，患者的 SLC20A2 发生了导致外显子 6 跳跃的突变。