Progressive osseous heteroplasia caused by a mosaic <i><scp>GNAS</scp></i> mutation

Pereda, Arrate; Martos-Tello, Jose Maria; Garin, Intza; Errea-Dorronsoro, Javier; Nanclares, Guiomar Perez de

doi:10.1111/cen.13584

Cited by 5 publications

(10 citation statements)

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“…GNAS gene encodes for the main transcript, the one coding for the alpha subunit of the stimulatory G protein (G s α), a signalling protein necessary for the actions of numerous hormones, neurotransmitters and autocrine/paracrine factors. 1 The G s α deficiency leads to the differentiation of osteoblasts in extraskeletal connective tissues that produce islands of ectopic membranous bone. 2 Inactivating genetic variants (including point mutations and genomic rearrangements) affecting this transcript may manifest with ectopic ossification and hormone resistance depending on the parent-of-origin allele affected (Table 1).…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…Work‐up revealed normal levels of calcium, phosphate, parathyroid hormone (PTH), FT3, FT4 and thyroid‐stimulating hormone (TSH). Sequencing analysis of the GNAS gene revealed a de novo heterozygous pathogenic variant c.568_571delGACT p.(Asp190Metfs*14), which was confirmed to be at her paternal allele by allele‐specific reverse transcription polymerase chain reaction 1 . No brachydactyly was found on radiological examination of hand and feet.…”

Section: Case Reportmentioning

confidence: 96%

“…(Asp190Metfs*14), which was confirmed to be at her paternal allele by allele-specific reverse transcription polymerase chain reaction. 1 No brachydactyly was found on radiological examination of hand and feet.…”

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confidence: 98%

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Congenital cutaneous ossification

Gomes

Kieselova

Santiago

et al. 2021

J Paediatrics Child Health

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Case Reportmentioning

confidence: 96%

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confidence: 98%

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Congenital cutaneous ossification

Gomes

Kieselova

Santiago

et al. 2021

J Paediatrics Child Health

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“…Multiple congenital skeletal malformations are associated with FOP, most frequently including an abnormal first toe (6), dysmorphology affecting the digits of the hand (7) and malformations of the cervical spine. POH is a genetic disease that has a predilection for the skin and subcutis characterized by plaque-like HO, beginning in infancy in the dermis and subsequently developing to involve deep connective tissues, such as the muscles and joints, which sometimes leads to loss of mobility (8). However, a loss-of-function mutation in guanine nucleotide binding protein G subunit α, an imprinted gene, is responsible for POH (9–11).…”

Section: Introductionmentioning

confidence: 99%

Targeting heterotopic ossification by inhibiting activin receptor‑like kinase 2 function (Review)

et al. 2019

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Heterotopic ossification (Ho) refers to the appearance of osteoblasts in soft tissues under pathological conditions, such as trauma or infection. Ho arises in an unpredictable way without any recognizable initiation. activin receptor-like kinase-2 (alK2) is a type i cell surface receptor for bone morphogenetic proteins (BMPs). The dysregulation of alK2 signaling is associated with a variety of diseases, including cancer and Ho. at present, the prevention and treatment of Ho in the clinic predominantly includes nonsteroidal anti-inflammatory drugs (NSAIDs), bisphosphonates and other drug treatments, low-dose local radiation therapy and surgical resection, rehabilitation treatment and physical therapy. However, most of these therapies have adverse effects. These methods do not prevent the occurrence of Ho. The pathogenesis of HO is not being specifically targeted; the current treatment strategies target the symptoms, not the disease. These treatments also cannot solve the fundamental problem of the occurrence of Ho. Therefore, scholars have been working to develop targeted therapies based on the pathogenesis of Ho. The present review focuses on advances in the understanding of the underlying mechanisms of Ho, and possible options for the prevention and treatment of Ho. in addition, the role of alK2 in the process of Ho is introduced and the progress made towards the targeted inhibition of alK2 is discussed. The present study aims to offer a platform for further research on possible targets for the prevention and treatment of Ho. Contents 1. introduction 2. BMP family and pathway 3. Structure of alK2 4. alK2 signaling pathway in Ho 5. development of treatments for Ho by targeting alK2 6. conclusion and prospects

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Progressive osseous heteroplasia in a 5-year-old boy with a novel mutation in exon 2 of GNAS: a case presentation and literature review

Sun

et al. 2023

BMC Musculoskelet Disord

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Background 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. Case presentation 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. Conclusion 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.

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Progressive osseous heteroplasia caused by a mosaic GNAS mutation

Cited by 5 publications

References 5 publications

Congenital cutaneous ossification

Congenital cutaneous ossification

Targeting heterotopic ossification by inhibiting activin receptor‑like kinase 2 function (Review)

Progressive osseous heteroplasia in a 5-year-old boy with a novel mutation in exon 2 of GNAS: a case presentation and literature review

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