Objective: The aim of this study is to evaluate the diagnostic value of whole exome sequencing in Chinese patients with brain calcification, and to provide exome sequencing-based insights into the genetic mechanisms of brain calcification to help establish accurate diagnoses, design appropriate treatments and assist in genetic counselling.

Background: Intracranial calcification is one of the common neuroimaging signs. The occurrence of intracranial calcification is associated with age, ranging from 1% in the young to 20.6% in the elderly. Intracranial calcification is highly heterogeneous clinically, some patients can present with a gradually progressive movement disorder and neuropsychiatric symptoms. Genetic mutations have been reported as triggering or risk factors for a large proportion of brain calcification.

Method: We collected whole blood samples of 968 individuals from 584 family with brain calcification,  whole exome sequencing was performed and analysed on 584 proband with brain calcification. The clinical phenotypes and family history of every proband were also analysed.

Results: Most variants found in brain calcification patients were associated with primary familial brain calcification. The most frequently variant found was in SLC20A2(86/584, 14.72%), heterozygous variants of MYORG(15/584, 2.56%), homozygous or compound heterozygous variant MYORG(12/584, 2.05%), PDGFB(5/584, 0.86%), PDGFRB(7/584, 1.20%), XPR1(4/584, 0.68%), and followed by homozygous or compound heterozygous variant JAM2(3/584, 0.51%). Except for primary familial brain calcification, there were also other genes identified, such as PANK2 which was associated with neurodegeneration with brain iron accumulation, IFIH1 and TREX1 which associated with Aicardi-Goutieres syndrome.

Conclusion: About 23.8% proband with brain calcification was diagnosed with genetic cause. And the primary familial brain calcification was most common genetic cause in Chinese patients with brain calcification. In addition, the detection of serum calcium, phosphorus levels and parathyroid hormone levels is helpful for the diagnosis of severe intracranial calcification. Bilateral globus pallidum punctate calcification requires brain MRI to distinguish from iron deposition disease.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/exome-sequencing-of-584-chinese-proband-with-brain-calcification/