Biallelic Mutations in MYORG Cause Autosomal Recessive Primary Familial Brain Calcification
| Autor: | Yao Xiangping, Shuang Wu, Xue-Jiao Chen, Hui-Zhen Su, Ning Wang, Wan-Jin Chen, Lu-Lu Lai, Xiaojuan Li, Yu-Ying Zhao, Chong Wang, Xuewen Cheng, Hongjie Yu, Miao Zhao, Jianfeng Xu, Zhi-Qi Xiong, Xin-Xin Guo, Xiao-Huan Zou, Ying-Qian Lu, En-Lin Dong, Gaofeng Fan |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Male Pathology medicine.medical_specialty Cerebral calcification Glycoside Hydrolases Basal ganglia calcification Biology Compound heterozygosity Pathogenesis 03 medical and health sciences Mice 0302 clinical medicine Calcinosis Loss of Function Mutation medicine Animals Humans RNA Messenger Gene Alleles Aged Mice Knockout Brain Diseases Genetic heterogeneity General Neuroscience Middle Aged medicine.disease Pedigree 030104 developmental biology Astrocytes Case-Control Studies Mutation Female 030217 neurology & neurosurgery Calcification |
| Zdroj: | Neuron. 98(6) |
| ISSN: | 1097-4199 |
| Popis: | Summary 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 S100β-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. |
| Databáze: | OpenAIRE |
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