A splice site mutation causing exon 6 skipping in SLC20A2 gene in a primary familial brain calcification family
| Autor: | Lihua Zhang, Hong-Hao Zhou, Guo-Ying Zou, Yuan-Tao Huang, Lin Cheng, Mei-Fang Li |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine Proband PDGFRB Biology medicine.disease_cause 03 medical and health sciences symbols.namesake Exon 0302 clinical medicine Asian People Exome Sequencing medicine Humans Family Genetics Sanger sequencing Brain Diseases Mutation Splice site mutation Sodium-Phosphate Cotransporter Proteins Type III Genetic heterogeneity General Neuroscience Alternative splicing Brain Calcinosis Exons Middle Aged Pedigree 030104 developmental biology symbols Female RNA Splice Sites Xenotropic and Polytropic Retrovirus Receptor 030217 neurology & neurosurgery |
| Zdroj: | Brain Research Bulletin. 150:261-265 |
| ISSN: | 0361-9230 |
| DOI: | 10.1016/j.brainresbull.2019.01.006 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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