Martínez-Gil Núria, Mellibovsky Leonardo, Manzano-López González Demián, Patiño Juan David, Cozar Monica, Rabionet Raquel, Grinberg Daniel, Balcells Susanna
Department of Genetics, Microbiology and Statistics, Faculty of Biology, Universitat de Barcelona, CIBERER, IBUB, IRSJD, Barcelona, Spain.
Musculoskeletal Research Group, IMIM (Hospital del Mar Medical Research Institute), Centro de Investigación Biomédica en Red en Fragilidad y Envejecimiento Saludable (CIBERFES), ISCIII, Barcelona, Spain.
Bone Rep. 2022 Mar 15;16:101181. doi: 10.1016/j.bonr.2022.101181. eCollection 2022 Jun.
Chiari malformation type 1 (C1M) is a neurological disease characterized by herniation of the cerebellar tonsils below the foramen magnum. Cranial bone constriction is suspected to be its main cause. To date, genes related to bone development (e.g. or ) have been associated with C1M, while some bone diseases (e.g. Paget) have been found to cosegregate with C1M. Nevertheless, the association between bone mineral density (BMD) and C1M has not been investigated, yet. Here, we systematically investigate the association between C1M and BMD, and between bone related genes and C1M.
We have recruited a small cohort of C1M patients (12 unrelated patients) in whom we have performed targeted sequencing of an in-house bone-related gene panel and BMD determination through non-invasive DXA.
In the search for association between the bone related genes and C1M we have found variants in more than one C1M patient in , , and . These genes have been either associated with craniofacial development in different ways, or previously associated with C1M (). Regarding the potential link between BMD and C1M, we have found three osteoporotic patients and one patient who had high BMD, very close to the HBM phenotype values, although most patients had normal BMD.
Variants in bone related genes have been repeatedly found in some C1M cases. The relationship of bone genes with C1M deserves further study, to get a clearer estimate of their contribution to its etiology. No direct correlation between BMD and C1M was observed.
1型Chiari畸形（C1M）是一种神经疾病，其特征为小脑扁桃体疝入枕骨大孔以下。颅骨狭窄被怀疑是其主要病因。迄今为止，与骨骼发育相关的基因（如 或 ）已与C1M相关联，同时发现一些骨病（如佩吉特病）与C1M共分离。然而，骨矿物质密度（BMD）与C1M之间的关联尚未得到研究。在此，我们系统地研究C1M与BMD之间以及骨相关基因与C1M之间的关联。
我们招募了一小群C1M患者（12名无亲缘关系的患者），对其进行了内部骨相关基因 panel 的靶向测序，并通过非侵入性双能X线吸收法（DXA）测定了BMD。
在寻找骨相关基因与C1M之间的关联时，我们在 、 、 和 中发现不止一名C1M患者存在变异。这些基因要么以不同方式与颅面发育相关，要么先前与C1M相关（ ）。关于BMD与C1M之间的潜在联系，我们发现了三名骨质疏松患者和一名BMD非常高的患者，其值非常接近高骨量（HBM）表型值，尽管大多数患者的BMD正常。
在一些C1M病例中反复发现骨相关基因的变异。骨基因与C1M的关系值得进一步研究，以更清楚地评估它们在其病因学中的作用。未观察到BMD与C1M之间的直接相关性。
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