Two Chinese Research Institutions to Transfer PFBC Genetic Testing Technology for RMB 50,000

Recently, the First Affiliated Hospital of Fujian Medical University and the Center for Excellence in Brain Science and Intelligence Technology of the Chinese Academy of Sciences released a public notice on the transformation of scientific and technological achievements, proposing to transfer them through listed trading.“Human PFBC Pathogenic Gene MYORG with Mutations at Sites 348-349 and Its Application”Relevant patents were assigned to the industry party, with a total transaction amount of RMBRMB 50,000. The inventor of this patented technology isWang Ning and Zhao Miao。

This Patent DiscoveryMYORG GeneIdentified as the autosomal recessive disease-causing gene for Primary Familial Brain Calcification (PFBC), nine pathogenic mutation forms of this gene were characterized, and corresponding detection kits and methods were developed, providing critical support for the diagnosis, pathogenesis research, and drug development of PFBC.

Primary Familial Brain Calcification (PFBC), as a hereditary neurological disorder with insidious progression, is characterized byBilateral Symmetrical Brain Calcificationas its primary characteristics. Patients typically develop the condition in middle age, and after onset, they are highly susceptible to severe symptoms such as motor impairments, cognitive decline, and even dementia, which undoubtedly imposes a heavy burden on patients’ families and the healthcare system.

This disease exhibits significant clinical heterogeneity; patients with mild symptoms may present no obvious manifestations, whereas those with severe symptoms experience rapid disease progression. Although cranial CT can detect calcifications, it is difficult to achieve early definitive diagnosis and identify the underlying etiology, causing most patients to miss the optimal window for intervention.

The Diagnostic and Therapeutic Dilemma of PFBCIt is highly significant in clinical practice. In the early stages of the disease, patients typically present with dizziness and mild limb tremors, which are easily confused with conditions such as Parkinson’s disease and cerebrovascular disorders; routine examinations often fail to differentiate them. By the time typical calcification foci appear, the brain damage has become irreversible.

Furthermore, this disease exhibitsFamily Genetic Predisposition, traditional detection methods are unable to accurately identify carriers of pathogenic genes, making it difficult to conduct prenatal diagnosis and provide eugenic guidance, which leads to the continuous transmission of pathogenic genes within families.

For confirmed patients, current clinical practice can only alleviate symptoms through symptomatic treatment; there is a lack of etiology-targeted curative therapies, unable to halt the progression of cerebral calcification, ultimately placing patients at risk of losing their ability to perform activities of daily living.

There are numerous pressing challenges in the current diagnosis and treatment of PFBC that urgently require breakthroughs.At the diagnostic level,Conventional diagnostic methods primarily rely on cranial CT imaging features and family history for inference. Due to the lack of specific molecular biomarkers, the misdiagnosis rate is relatively high. Furthermore, the limited coverage of known pathogenic gene testing fails to encompass all genetic subtypes, making it difficult to accurately identify a large number of patients with recessive inherited disorders.

In terms of treatment,Currently, there are no medications capable of halting or reversing the process of intracranial calcium salt deposition. Existing symptomatic treatments can only provide temporary relief and cannot alter the disease progression. Furthermore, due to the incompletely elucidated pathogenesis, drug development lacks clear therapeutic targets, leaving a long-standing gap in relevant treatment options.

Meanwhile,Genetic Heterogeneity of PFBCexacerbating the difficulty of diagnosis and treatment. Significant heterogeneity exists in pathogenic genes and clinical phenotypes among patients from different families, making it difficult for traditional single-modality testing methods to achieve comprehensive coverage. For high-risk populations with a family history, there is currently a lack of convenient and precise screening tools, thereby hindering early warning and intervention.

These challenges have created an urgent clinical need for precise molecular diagnostic technologies and targeted therapeutic regimens to address the industry-wide hurdles in the diagnosis and treatment of PFBC, thereby providing patients with a comprehensive, end-to-end solution encompassing early screening, accurate diagnosis, and effective treatment.

To address industry challenges in primary familial brain calcification (PFBC), including incomplete coverage of pathogenic genes, low diagnostic accuracy, and unclear pathogenesis, the First Affiliated Hospital of Fujian Medical University and the Center for Excellence in Brain Science and Intelligence Technology of the Chinese Academy of Sciences have jointly developed“Technology of Human PFBC Pathogenic Gene MYORG with Mutations at Sites 348–349 and Its Applications”. This technology is based on“Analysis of Novel Pathogenic Genes + Construction of Proprietary Testing Systems” as the Core, leveraging the synergistic innovation of gene function and detection technologies, we have constructed a comprehensive framework covering“Precision Diagnosis + Mechanism Exploration + Drug Targets”an integrated solution that achieves comprehensive breakthroughs from etiologic analysis to clinical application, significantly enhancing the scientific rigor and practical utility of PFBC diagnosis and treatment.

The core advantage of this technology lies inFirst identification of the MYORG gene as the causative gene for autosomal recessive primary familial brain calcification (PFBC), filling the gap in research on the pathogenic mechanisms of the recessive inheritance subtype.Traditional studies have identified only four autosomal dominant disease-causing genes, leaving a large number of patients with autosomal recessive primary familial brain calcification (PFBC) without a precise diagnosis due to unknown etiologies.

Through systematic investigation of six families with primary familial brain calcification (PFBC), this invention identified nine pathogenic mutations in the MYORG gene, encompassing various mutation types such as base substitutions, insertions, and deletions, including nonsense and missense mutations. Notably, certain variants, such as the c.348_349insCTGGCCTTCCGC insertion, represent novel pathogenic sites newly discovered in this study.

These mutations trigger brain calcification by inducing astrocyte dysfunction and abnormal protein glycosylation metabolism, thereby revealing novel molecular mechanisms underlying the pathogenesis of primary familial brain calcification (PFBC) and providing new theoretical directions for disease research. Furthermore, it has been clarified that both homozygous and heterozygous forms of the mutated genes can lead to disease onset, offering a clear basis for the establishment of diagnostic criteria.

In the field of detection technology, innovative research and developmentProprietary Test Kits and Standardized Procedures, achieving highly efficient and precise detection of MYORG gene mutations. Traditional detection methods lack specific primers and assay systems, making it difficult to rapidly identify MYORG gene mutations.

The present invention relies onPCR Amplification and Sanger Sequencing Technology, three pairs of specific primers (SEQ ID NO: 21–26) were meticulously designed to selectively amplify gene fragments containing distinct mutation sites, thereby achieving precise coverage of all nine pathogenic mutations. The kit includes core components required for PCR reactions, such as DNA polymerase and buffer solutions, eliminating the need for additional preparation and thus simplifying the operational workflow.

The detection process involves only three steps: first, genomic DNA is extracted from body fluid samples such as blood and amniotic fluid; next, PCR amplification is performed using a kit; finally, the products are sequenced and compared with the wild-type sequence to clearly identify mutation information. The entire procedure is simple to operate and time-efficient, making it suitable for routine clinical testing and large-scale screening.

Following validation across six pedigrees and 1,000 healthy controls, the test demonstrated 100% accuracy, effectively differentiating patients from the normal population and providing reliable technical support for early diagnosis.

Furthermore, this technology has broad application scenarios, catering to both clinical diagnosis and treatment as well as scientific research needs, thereby offering multiple practical values.

At the clinical level,It can serve as a specific target for the molecular diagnosis of PFBC, enabling early definitive diagnosis in patients, screening of familial cases, and prenatal diagnosis, thereby supporting eugenics and healthy childbirth. The associated detection kit is easy to operate and cost-effective, making it suitable for promotion and application across medical institutions at all levels.

At the scientific research level,Mutant gene sequences, encoded proteins, and recombinant vectors can serve as core tools for studying the pathogenesis of primary familial brain calcification (PFBC), providing an experimental foundation for investigating astrocyte function and the role of the neurovascular unit. Meanwhile, the MYORG gene and its mutation sites can act as potential targets for drug development, offering clear direction for the research and development of targeted preventive and therapeutic agents.

Multiple design features further enhance the practicality of this technology: the assay is compatible with various bodily fluids, including blood and serum, to meet the needs of diverse clinical scenarios; the primers exhibit high specificity, effectively avoiding cross-reactivity and ensuring accurate detection results; and sequencing results are interpreted against a clearly defined wild-type reference sequence (SEQ ID NO: 1), facilitating standardized interpretation and lowering the operational threshold.

These advantages give this technology broad application prospects in the diagnosis and treatment of PFBC, providing strong support for precise disease prevention and control.

The market for genetic diagnosis of Primary Familial Brain Calcification (PFBC) has gradually emerged alongside deepening research into its pathogenic mechanisms. Domestic and international enterprises, as well as research institutions, have strategically focused on two core demands: “comprehensive coverage of pathogenic gene detection” and “precise and efficient detection technologies,” forming a competitive landscape characterized by “research-to-commercialization products + clinically applicable test kits.”

Thermo Fisher Scientific(Thermo Fisher Scientific) has launched the “Applied Biosystems™ Targeted Sequencing Panel for Genetic Disorders,” which includes a module for detecting pathogenic genes associated with PFBC. This product focuses on core pathogenic genes underlying neurological genetic disorders, employing customized probe capture technology to specifically enrich gene regions such as SLC20A2, XPR1, and MYORG, and integrates Sanger sequencing verification to achieve precise confirmation of mutation sites. Its core advantages lie in the high specificity of the probes and a detection sensitivity exceeding 99%. The accompanying TaqMan® SNP Detection Kit enables rapid screening of known mutation sites, making it suitable for routine clinical testing and large-scale population screening. The product has obtained CE marking and is widely used in clinical laboratories across multiple countries in Europe and Asia.

Germany's CENTOGENE CompanyAs a leading enterprise in the field of genetic diagnosis for rare diseases, we have launched the “Intracerebral Calcification Specialized Testing Panel,” which provides precise coverage of PFBC-related pathogenic genes.

This product encompasses 30 core genes associated with intracranial calcification, including classic autosomal dominant pathogenic genes such as SLC20A2, PDGFRB, PDGFB, and XPR1, as well as the autosomal recessive pathogenic gene MYORG, enabling comprehensive screening for multiple genetic subtypes in a single test.

The core advantages of the product lie in its high detection coverage, with ≥99% coverage of all target gene coding regions and flanking non-coding regions, a sequencing depth of ≥20×, support for copy number variation (CNV) analysis, and the ability to effectively identify various mutation types, including base substitutions, insertions and deletions, and gene fragment abnormalities.

The testing cycle is 25 working days, catering to the needs of clinical diagnosis and familial screening, and applicable to patients at different stages of disease onset, ranging from neonatal critical cases to adults with movement disorders and dementia.

Blueprint Genetics, FinlandFocusing on single-gene disorder testing, we have launched the “SLC20A2 Single-Gene Testing Service,” which provides precise detection of SLC20A2, the most common autosomal dominant pathogenic gene associated with Primary Familial Brain Calcification (PFBC). Leveraging next-generation sequencing technology, the product comprehensively covers all coding regions of the SLC20A2 gene, enabling effective identification of various pathogenic mutations that cause “Basal Ganglia Calcification Type 1.”

Furthermore, the SLC20A2 gene has been incorporated into the company’s “Ataxia Testing Panel” to facilitate differential diagnosis from other hereditary neurological disorders, thereby further expanding its clinical applications.