Biallelic Mutations in MYORG Cause Autosomal Recessive Primary Familial Brain Calcification

Biallelic Mutations in MYORG Cause Autosomal Recessive Primary Familial Brain Calcification

Abstract

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.

Authors: Yao XP1, Cheng X2, Wang C1, Zhao M1, Guo XX1, Su HZ1, Lai LL1, Zou XH1, Chen XJ3, Zhao Y4, Dong EL1, Lu YQ1, Wu S1, Li X5, Fan G5, Yu H6, Xu J6, Wang N7, Xiong ZQ8, Chen WJ9.

Influence Factor: 14.024

Citation: Neuron 98, 1116-1123.e1115 (2018).

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