Data_Sheet_1_Case Report: Two Monochorionic Twins With a Critically Different Course of Progressive Osseous Heteroplasia.PDF

Progressive osseous heteroplasia (POH; OMIM 166350) is a rare autosomal-dominant genetic disorder in which extra-skeletal bone forms within skin and muscle tissue. POH is one of the clinical manifestations of an inactivating mutation in the GNAS gene. GNAS gene alterations are difficult matter to address, as GNAS alleles show genetic imprinting and produce several transcript products, and the same mutation may lead to strikingly different phenotypes. Also, most of the publications concerning POH patients are either clinical depictions of a case (or a case series), descriptions of their genetic background, or a tentative correlation of both clinical and molecular findings. Treatment for POH is rarely addressed, and POH still lacks therapeutic options. We describe a unique case of POH in two monochorionic twins, who presented an almost asymptomatic vs. the severe clinical course, despite sharing the same mutation and genetic background. We also report the results of the therapeutic interventions currently available for heterotopic ossification in the patient with the severe course. This article not only critically supports the assumption that the POH course is strongly influenced by factors beyond genetic background but also remarks the lack of options for patients suffering an orphan disease, even after testing drugs with promising in vitro results.

进行性骨异位增生（POH；OMIM 166350）是一种罕见的常染色体显性遗传疾病，其特征在于骨骼组织在皮肤和肌肉组织中形成。POH是GNAS基因失活突变的一种临床表现。由于GNAS等位基因表现出遗传印记并产生多种转录产物，GNAS基因的变异处理颇具挑战性，且相同的突变可能导致截然不同的表型。此外，大多数关于POH患者的出版物要么是对病例（或病例系列）的临床描述，要么是对其遗传背景的描述，或者是临床和分子发现之间的初步关联。POH的治疗方案鲜有涉及，且该疾病仍缺乏有效的治疗选择。本文描述了一例双卵双生的独特病例，这对双胞胎尽管具有相同的突变和遗传背景，却表现出几乎无症状与严重病程之间的显著差异。我们还报告了针对病程严重患者的异位骨化目前可用的治疗干预措施。本文不仅从批判性角度支持了POH病程受遗传背景之外因素强烈影响的假设，而且指出即使药物在体外实验中表现出良好的结果，罕见病患者仍缺乏治疗选择。