Biallelic Mutations in MYORG Cause Autosomal Recessive Primary Familial Brain Calcification
Biallelic Mutations in MYORG Cause Autosomal Recessive Primary Familial Brain Calcification
复制标题
MYORG 的双等位基因突变导致常染色体隐性原发性家族性脑钙化
DOI：
10.1016/j.neuron.2018.05.037
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发表时间：
2018-06-27
期刊：
影响因子：
16.2
通讯作者：
Chen, Wan-Jin
中科院分区：
文献类型：
--
作者：
Yao, Xiang-Ping;Cheng, Xuewen;Chen, Wan-Jin
原发性家族性脑钙化（PFBC）是一种遗传异质性疾病，其特征是基底节和其他脑区域的双侧钙化。这种疾病的遗传基础在很大一部分家族性病例中仍然未知。在这里，我们报告了一个隐性致病基因，MYORG，PFBC。MYORG复合杂合或纯合突变与PFBC在6个家族中完全分离，在零重组分数下的比值对数（LOD）评分为4.91。在小鼠中，Myorg mRNA在S100b阳性星形胶质细胞中特异性表达，Myorg基因敲除诱导9月龄时脑钙化的形成。我们的研究结果提供了强有力的证据，证明MYORG的功能缺失突变会导致人类和小鼠的脑钙化。
Primary familial brain calcification (PFBC) is a genetically heterogeneous disorder characterized by bilateral calcifications in the basal ganglia and other brain regions. The genetic basis of this disorder remains unknown in a significant portion of familial cases. Here, we reported a recessive causal gene, MYORG, for PFBC. Compound heterozygous or homozygous mutations of MYORG co-segregated completely with PFBC in six families, with logarithm of odds (LOD) score of 4.91 at the zero recombination fraction. In mice, Myorg mRNA was expressed specifically in S100b-positive astrocytes, and knockout of Myorg induced the formation of brain calcification at 9 months of age. Our findings provide strong evidence that loss-of-function mutations of MYORG cause brain calcification in humans and mice.