Department of Immunology, Ministry of Education Key Laboratory of Major Diseases in Children, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No. 56 Nan Li Shi Lu, Beijing, 100045, China.
BMC Musculoskelet Disord. 2023 Mar 31;24(1):247. doi: 10.1186/s12891-023-06371-4.
Progressive osseous heteroplasia (POH) is a rare genetic condition that causes progressive ossification. This usually results from an inactivating mutation of the paternal GNAS gene. Herein, we report a case of POH caused by a novel mutation in exon 2 of the GNAS gene.
A 5-year-old Chinese boy was referred to our hospital for a growing mass in his right foot. Although laboratory findings were normal, radiographic imaging revealed severe ossification in his right foot and smaller areas of intramuscular ossification in his arms and legs. A de novo mutation (c.175C > T, p.Q59X) in exon 2 of the GNAS gene was identified, prompting a diagnosis of POH. We conducted a systematic literature review to better understand this rare disease.
We have discovered that a de novo nonsense mutation in exon 2 of GNAS can lead to POH. Our literature review revealed that ankylosis of the extremities is the primary clinical outcome in patients with POH. Unlike other conditions such as fibrodysplasia ossificans progressiva (FOP), patients with POH do not experience respiratory failure. However, much remains to be learned about the relationship between the type of GNAS gene mutation and the resulting POH symptoms. Further research is needed to understand this complex and rare disease. This case adds to our current understanding of POH and will contribute to future studies and treatments.
进行性骨化性异质增生症（POH）是一种罕见的遗传疾病，可导致进行性骨化。这通常是由于父系 GNAS 基因的失活突变引起的。在此，我们报告一例由 GNAS 基因外显子 2 中的新突变引起的 POH 病例。
一名 5 岁中国男孩因右脚肿块就诊于我院。尽管实验室检查结果正常，但影像学检查显示其右脚严重骨化，手臂和腿部有较小的肌肉内骨化区域。在外显子 2 中发现了一个新的突变（c.175C>T，p.Q59X），提示诊断为 POH。我们进行了系统的文献回顾，以更好地了解这种罕见疾病。
我们发现 GNAS 外显子 2 中的一个新的无义突变可导致 POH。我们的文献回顾表明，四肢僵硬是 POH 患者的主要临床结局。与纤维发育不良性骨化过度症（FOP）等其他疾病不同，POH 患者不会发生呼吸衰竭。然而，关于 GNAS 基因突变类型与 POH 症状之间的关系，还有很多需要了解。需要进一步研究以了解这种复杂而罕见的疾病。本病例增加了我们对 POH 的现有认识，并将有助于未来的研究和治疗。
