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Clinical, Biochemical, Radiological, and Genetic Analyses of a Patient with VCP Gene Variant-Induced Paget’s Disease of Bone

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Abstract

Paget’s disease of bone (PDB) is a rare metabolic bone disorder, which is extremely rare in Asian population. This study aimed to investigate the phenotypes and the pathogenic mutations of woman with early-onset PDB. The clinical features, bone mineral density, x-ray, radionuclide bone scan, and serum levels of alkaline phosphatase (ALP), procollagen type 1 N-terminal propeptide (P1NP), and β-carboxy-terminal cross-linked telopeptide of type 1 collagen (β-CTX) were measured in detail. The pathogenic mutations were identified by whole-exon sequencing and confirmed by Sanger sequencing. We also evaluated the effects of intravenous infusion of zoledronic acid on the bones of the patient and summarized the phenotypic characteristics of reported patients with mutation at position 155 of the valosin-containing protein (VCP). The patient only exhibited bone pain as the initial manifestation with vertebral compression fracture and extremely elevated ALP, P1NP, and β-CTX levels; she had no inclusion body myopathy and frontotemporal dementia. The missense mutation in exon 5 of the VCP gene (p.Arg155His) was identified by whole-exome sequencing and further confirmed by Sanger sequencing. No mutation in candidate genes of PDB, such as SQSTM1, CSF1, TM7SF4, OPTN, PFN1, and TNFRSF11A, were identified in the patient by Sanger sequencing. Rapid relief of bone pain and a marked decline in ALP, P1NP, and β-CTX levels were observed after zoledronic acid treatment. Previously reported patients with VCP missense mutation at position 155 (R155H) always had myopathy, frontotemporal dementia, and PDB, but the patient in this study exhibited only PDB. This was the first report of R155H mutation-induced early-onset in the VCP gene in Asian population. PDB was the only manifestation having a favorable response to zoledronic acid treatment. We broadened the genetic and clinical phenotype spectra of the VCP mutation.

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Acknowledgements

We appreciate the patient and her family for their participation in the study.

Funding

This work is supported by National Natural Science Foundation of China (Nos.81873668, 82070908), Beijing Natural Science Foundation (7202153), and National Key R&D Program of China (2018YFA0800801).

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Authors and Affiliations

  1. Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Shuaifuyuan No.1, Dongcheng District, Beijing, 100730, China

    Yongze Zhang, Qian Zhang, Ou Wang, Yan Jiang, Xiaoping Xing, Weibo Xia & Mei Li

  2. Department of Orthopedics, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Shuaifuyuan No.1, Dongcheng District, Beijing, 100730, China

    Peng Gao

  3. Department of Endocrinology, The First Affiliated Hospital of Fujian Medical University, 20 Cha Zhong Road, Fuzhou, 350005, Fujian, China

    Yongze Zhang & Sunjie Yan

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  1. Yongze Zhang
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Correspondence to Mei Li.

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Disclosure

Yongze Zhang, Peng Gao, Sunjie Yan, Qian Zhang, Ou Wang, Yan Jiang, Xiaoping Xing, Weibo Xia, and Mei Li declare that they have no conflict of interest.

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All procedures were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration.

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Informed consent was obtained from the proband in the study. The study protocol was approved by the Scientific Research Ethics Committee of PUMCH.

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Zhang, Y., Gao, P., Yan, S. et al. Clinical, Biochemical, Radiological, and Genetic Analyses of a Patient with VCP Gene Variant-Induced Paget’s Disease of Bone. Calcif Tissue Int 110, 518–528 (2022). https://doi.org/10.1007/s00223-021-00929-x

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