背景:透明纤维瘤病综合征是一种由ANTXR2致病变异引起的罕见常染色体隐性遗传疾病。该疾病的特征在于结缔组织中无定形透明物质的沉积。这种疾病的标志是关节挛缩,广义皮肤僵硬度,关节伸肌表面色素沉着过度的丘疹,肉质肛周肿块,严重的腹泻,牙龈肥大.疾病的严重程度各不相同,预后较差。目前还没有具体的治疗方法。大多数患有严重疾病的患者在第二年之前去世。在这项研究中,我们描述了在土耳其一个三级参考中心诊断和随访的7例透明纤维瘤病综合征患者的临床和分子结果.
方法:采用标准盐析法从3例患者外周血中提取基因组DNA。在一名患者中,由于无法获得外周血DNA,因此在病理载玻片上进行了DNA提取。在ABIPrism3500遗传分析仪上扩增和测序ANTXR2的所有编码外显子。
结果:在3例患者中进行了Sanger测序,纯合c.945T>Gp。(Cys315Trp),c.1073dupp.(Ala359CysfsTer13),和c.1074delp.(Ala359HisfsTer50)变体在ANTXR2中鉴定。所有患者在5岁之前去世。
结论:HFS是一种罕见的,具有广泛表型谱的进行性疾病。HFS易于识别,具有独特的临床特征。然而,由于严重的临床代偿失调,预后差,死亡率增加.
BACKGROUND: Hyaline fibromatosis syndrome is a rare autosomal recessive disorder caused by ANTXR2 pathogenic variants. The disorder is characterized by the deposition of amorphous hyaline material in connective tissues. The hallmarks of the disease are joint contractures, generalized skin stiffness, hyperpigmented papules over extensor surfaces of joints, fleshy perianal masses, severe diarrhea, and gingival hypertrophy. The severity of the disease varies and prognosis is poor. No specific treatment is yet available. Most patients with the severe form of the condition pass away before the second year of age. In this study, we describe the clinical and molecular findings of a cohort of seven hyaline fibromatosis syndrome patients who were diagnosed and followed up at a single tertiary reference center in Turkey.
METHODS: Genomic DNA was extracted by standard salting out method from peripheric blood samples of three patients. In one patient DNA extraction was performed on pathology slides since peripheric blood DNA was not available. All coding exons of the ANTXR2 were amplified and sequenced on ABI Prism 3500 Genetic Analyser.
RESULTS: Sanger sequencing was performed in 3 patients and homozygous c.945T>G p.(Cys315Trp), c.1073dup p.(Ala359CysfsTer13), and c.1074del p.(Ala359HisfsTer50) variants were identified in ANTXR2. All patients passed away before the age of five years.
CONCLUSIONS: HFS is a rare, progressive disorder with a broad phenotypic spectrum. HFS can be recognized easily with distinctive clinical features. Nevertheless, it has poor prognosis with increased mortality due to severe clinical decompensation.