BACKGROUND: Idiopathic basal ganglia calcification (IBGC) is a neurodegenerative disease characterized by symmetrical calcification of basal ganglia and other brain region, also known as Fahr\'s disease. It can be sporadic or familial, and there is no definite etiology at present. With the development of neuroimaging, the number of reports of IBGC has increased in recent years. However, due to its hidden onset, diverse clinical manifestations, and low incidence, it is likely to be misdiagnosed or ignored by potential patients and their family.
METHODS: We report a case of a 61-year-old man who presented with symptoms of dysphagia and alalia. His computed tomography scan of the brain revealed bilateral symmetric calcifications of basal ganglia, cerebellum, thalamus, and periventricular area. The genetic test showed a new mutation sites of MYORG, c.1438T>G mutation and c.1271_1272 TGGTGCGC insertion mutation. He was finally diagnosed with IBGC.
CONCLUSIONS: It is important to detect MYORG mutation when IBGC is suspected, especially in those without an obvious family history, for better understanding of the underlying mechanism and identifying potential treatments.

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.
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.
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.
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.

BACKGROUND: Idiopathic basal ganglia calcification (IBGC) is a genetic disorder characterized by bilateral basal ganglia calcification and neural degeneration. In this study, we reported a new SLC2OA2 mutation of IBGC and reviewed relevant literature to explore the association between phenotypes and genotypes in Chinese IBGC patients.
METHODS: Clinical information of the proband and her relatives were collected comprehensively. Blood samples of both the patient and her father were obtained, and genetic screening related to IBGC was performed using second generation sequencing with their consent. Findings were confirmed by Sanger sequencing. Polyphen-2 was used to predict the potential association between mutations and disease. Then, we retrieved literatures of Chinese IBGC patients and explored the association between phenotype and genotype.
RESULTS: A novel mutation was identified through genetic testing, and it is suggested to be a damage mutation predicted by Polyphen-2. Through literature review, we found that SLC20A2 mutation is the most common cause for IBGC in China. Its hot spot regions are mainly on the 1st and 8th exons; the second common one is PDGFB where the hot spot covered a length of 220-230 bp localized on the 2nd exon; moreover, Chinese IBGC patients featured early-onset, more severe movement disorder and relatively mild cognitive impairment compared with those in other countries.
CONCLUSIONS: There is significant heterogeneity both in phenotype and genotype in Chinese IBGC patients. Further research of pathogenic mechanism of IBGC is required to eventually develop precise treatment for individuals who suffered this disease.
SLC20A2基因突变相关家族性特发性基底节钙化新位点报道及中国患者不同基因型导致的特发性基底节钙化临床特点分析摘要背景：特发性基底节钙化是以双侧基底节钙化和神经系统退行性病变为特征的遗传相关性疾病。本文我们报道了一个SLC20A2相关家族性特发性基底节钙化的新发位点，回顾并总结已经报道的上述各个基因型相关中国患者特发性基底节钙化的临床特点。 方法：首先，全面收集本家系先证者和家系成员的临床资料，包括病史、实验室检查和诊断相关的影像学资料。在取得相关人员知情同意的前体现，收集先证者和其父亲的外周血标本，并进行特发性基底节钙化相关基因的筛查。基因突变结果在家系内经一代测序验证，与表型共分离，并通过Polyphen-2软件预测极有可能为致病突变。其次，检索已经报道的中国特发性基底节病变的相关报道，总结不同基因型特发性基底节钙化的临床特点。 结果：通过基因测序、家系内验证和蛋白功能预测，我们发现一个导致特发性基底节钙化的SLC20A2基因新位点。通过分析总结文献，我们发现SLC20A2突变是中国单基因特特发性基底节钙化最常见的原因，其突变热点位于第一和第八号外显子区域。其次是PDGFB基因， 其突变热点位于二号外显子上长度为220-230bp的特定区域。此外，中国特发性基底节钙化的患者多表现为发病年龄早、运动症状较重、认知损害较轻。 结论：中国特发性基底节钙化患者表型和基因型均存在异质性，但也存在一定共性。在遗传突变基础上进一步机制研究能够帮助我能更清晰的了解疾病的发病机制，从而为不同基因型患者提供个体化治疗。.

BACKGROUND: Until recently, primary familial brain calcification (PFBC) has been determined by four genes, SLC20A2, PDGFRB, PDGFB and XPR1. No studies have been carried out to analyze the gene mutation of PDGFB in Chinese population.
OBJECTIVE: To screen mutations of PDGFB gene in a large cohort of Chinese PFBC patients with no SLC20A2 mutations.
METHODS: We recruited 192 PFBC patients, including 21 index cases and 171 sporadic cases, in our study. Peripheral venous blood samples of all included participants were collected for genomic DNA extraction. The coding sequence of PDGFB was amplified by polymerase chain reaction (PCR) followed by direct sequencing. The potential effects of the identified variants on protein function were assessed by bioinformatics analysis.
RESULTS: Three missense variants (c.35G>T, c.232C>T, and c.610C>A) and one nonsense variant (c.220G>T) of PDGFB were identified in five sporadic PFBC patients. The variant c.35G>T was found in 2 healthy controls from the same ethnic background, whereas c.220G>T, c.232C>T and c.610C>A were absent from 500 controls. c.220G>T (p.E74*) produced a stop codon in the place of the glutamicacid residue number 74. c.232C>T (p.R78C) occurred at highly conserved regions and were predicted as damaging by at least two computational predictive programs, suggesting that this variant were likely to have a causal role in PFBC. Although variant c.610C>A (p.P204T) also occurred at a highly conserved region, it was predicted to be most likely benign by two computational predictive programs, suggesting an uncertain role of this variant on PFBC.
CONCLUSIONS: The present study identified one likely pathogenic variant (p.E74*) and two variants of uncertain significance (p.R78C and p.P204T) in PDGFB. Further studies of PDGF-B functional expression for these variants are still required to confirm the pathogenic effect.

Idiopathic basal ganglia calcification (IBGC) is a rare neurodegenerative disorder characterized by the deposition of calcium in the brain and variable combinations of movement disorders, gait impairment and neuropsychiatric symptoms. Few reports have described psychiatric manifestations as early symptoms of IBGC. The present study reports the case of a middle-aged man with schizophrenia-like psychosis and obsessive-compulsive symptoms as the first manifestations of IBGC. The response of the patient to olanzapine and fluoxetine suggests that low-dose olanzapine is effective and should be increased cautiously to avoid worsening parkinsonism and that fluoxetine is an effective drug for the treatment of obsessive-compulsive symptoms in IBGC.

Idiopathic basal ganglia calcification (IBGC) is a rare neuropsychiatric disorder characterized by bilateral and symmetric cerebral calcifications. Recently, SLC20A2 was identified as a causative gene for familial IBGC, and three mutations were reported in a northern Chinese population. Here, we aimed to explore the mutation spectrum of SLC20A2 in a southern Chinese population. Sanger sequencing was employed to screen mutations within SLC20A2 in two IBGC families and 14 sporadic IBGC cases from a southern Han Chinese population. Four novel mutations (c.82G>A p.D28N, c.185T>C p.L62P, c.1470_1478delGCAGGTCCT p.Q491_L493del and c.935-1G>A) were identified in two families and two sporadic cases, respectively; none were detected in 200 unrelated controls. No mutation was found in the remaining 12 patients. Different mutations may result in varied phenotypes, including brain calcification and clinical manifestations. Our study supports the hypothesis that SLC20A2 is a causative gene of IBGC and expands the mutation spectrum of SLC20A2, which facilitates the understanding of the genotype-phenotype correlation of IBGC.