Lin Zhiru, Yang Dehao, Wang Lebo, Li Jiaxiang, Chen Xinhui, Jin Nan, Kang Yixin, Wang Xinchen, Fu Feng, Wang Haotian, Zheng Xiaosheng, Xie Fei, Cen Zhidong, Luo Wei
Department of Neurology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Neurology, Wenzhou Central Hospital, Wenzhou, China.
Mov Disord. 2025 Apr 19. doi: 10.1002/mds.30207.
Primary brain calcification (PBC) is a monogenic inherited disease characterized by calcifications in basal ganglia and other brain regions, with seven causative genes identified and highly heterogeneous genetic and phenotypic spectrum.
The objective was to update the genetic and phenotypic spectrum of PBC in a large cohort from China.
Five hundred eighty-four PBC families were enrolled. Brain calcification was assessed by total calcification score (TCS). Sanger sequencing of SLC20A2 and whole-exome sequencing were performed. Variants were classified by the American College of Medical Genetics and Genomics guidelines.
Eighty-eight probands were genetically diagnosed with pathogenic or likely pathogenic variants in SLC20A2 (75.86%), PDGFRB (2.30%), PDGFB (3.45%), XPR1 (3.45%), MYORG (11.49%), JAM2 (3.45%), and NAA60 (1.15%). Totally, 29 unreported variants were detected. Autosomal recessive PBC (AR-PBC) patients exhibited a higher rate of clinical symptoms compared to those with autosomal dominant PBC (AD-PBC) (100.00% vs. 55.06%, P < 0.001). In all PBC, advancing age showed associations with headache/dizziness (odds ratio [OR] = 0.97, P = 0.0241), cognitive dysfunction (OR = 1.07, P = 0.0025), and psychiatric symptoms (OR = 1.05, P = 0.0396). Regional calcification analysis showed that thalamic calcification scores were associated with cognitive impairment (OR = 1.34, P = 0.0026), followed by lenticular nucleus calcification with headache/dizziness (OR = 1.55, P = 0.0046), cerebellar hemisphere calcification with motor symptoms (OR = 1.45, P = 0.0051), and caudate nucleus calcification with psychiatric manifestations (OR = 1.2, P = 0.0351).
This large-scale Chinese cohort study demonstrates the genetic spectrum of PBC and phenotypic characteristics in genetically diagnosed PBC, and also provides genotype-imaging-symptom correlations of PBC. © 2025 International Parkinson and Movement Disorder Society.
原发性脑钙化（PBC）是一种单基因遗传病，其特征为基底节及其他脑区钙化，已鉴定出7个致病基因，遗传和表型谱高度异质性。
旨在更新来自中国的一个大型队列中PBC的遗传和表型谱。
纳入584个PBC家系。通过总钙化评分（TCS）评估脑钙化情况。对SLC20A2进行桑格测序并进行全外显子测序。变异按照美国医学遗传学与基因组学学会指南进行分类。
88名先证者经基因诊断在SLC20A2（75.86%）、PDGFRB（2.30%）、PDGFB（3.45%）、XPR1（3.45%）、MYORG（11.49%）、JAM2（3.45%）和NAA60（1.15%）中存在致病或可能致病的变异。共检测到29个未报道的变异。与常染色体显性PBC（AD-PBC）患者相比，常染色体隐性PBC（AR-PBC）患者临床症状发生率更高（100.00% 对55.06%，P < 0.001）。在所有PBC患者中，年龄增长与头痛/头晕相关（优势比[OR]=0.97，P = 0.0241）、认知功能障碍（OR = 1.07，P = 0.0025）和精神症状（OR = 1.05，P = 0.0396）。区域钙化分析显示，丘脑钙化评分与认知障碍相关（OR = 1.34，P = 0.0026），其次是豆状核钙化与头痛/头晕相关（OR = 1.55，P = 0.0046），小脑半球钙化与运动症状相关（OR = 1.45，P = 0.0051），尾状核钙化与精神症状相关（OR = 1.2，P = 0.0351）。
这项大规模中国队列研究展示了PBC的遗传谱以及基因诊断的PBC的表型特征，还提供了PBC的基因型-影像学-症状相关性。© 2025国际帕金森和运动障碍协会。
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