Amyloidosis-related nephrotic syndrome due to a G654A gelsolin mutation: the first report from the Middle East
Amyloidosis-related nephrotic syndrome due to a G654A gelsolin mutation: the first report from the Middle East
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DOI：
10.1093/ndt/gfl548
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发表时间：
2007-01-01
影响因子：
6.1
通讯作者：
Kiuru-Enari, Sari
中科院分区：
文献类型：
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作者：
Ardalan, Mohammad Reza;Shoja, Mohammadali Mohajel;Kiuru-Enari, Sari
一些基因突变与肾病综合征有关，包括产生nephrin、podocin、α actin -4、一种固定CD-2的适配器蛋白、典型瞬时受体电位-6和层粘连蛋白β -2[1]的基因突变。G654A凝胶蛋白基因突变也被发现与纯合子患者[2]的严重肾病综合征有关。这种突变导致形成构象异常的凝胶蛋白[3,4]。凝胶蛋白功能受损，加上突变凝胶蛋白的裂解产生淀粉样蛋白肽，导致一系列的表现，被称为凝胶相关淀粉样变性，AGel淀粉样变性，或最初被称为家族性淀粉样变性，芬兰型[5]。作者认为，将这种疾病单独称为淀粉样变会破坏其一些重要的致病方面。由于凝胶蛋白功能受损被认为在这种疾病的过程中起着关键作用，甚至在淀粉样变发生之前，我们在本文中使用了术语凝胶蛋白营养不良和淀粉样变性疾病（GDAD）。GDAD是一种常染色体显性全身性疾病，具有完全浸润性，于1969年由芬兰的Joko Meretoja首次描述。GDAD的主要临床表现为角膜晶格营养不良，进行性颅脑和周围神经病变以及皮肤松弛，尽管每个身体器官都可能受到影响[5-7]。该疾病较少见的表现包括但不限于：巨舌症、内分泌疾病、骨质疏松症、步态共济失调、自主神经功能障碍、心肌病、糖尿病和白内障[5,6]。GDAD偶尔会累及肾脏，通常表现为间歇性蛋白尿[6,7]。这种疾病最初被认为仅限于芬兰。然而，后来在欧洲其他地区发现了几种；丹麦、荷兰、前捷克斯洛伐克以及美国和日本。远东与欧洲、非洲和南美洲之间的大片地区没有GDAD的记录。我们报告一个淀粉样变的病人，他表现为肾病综合征。进一步的调查发现了G654A凝胶蛋白突变，并发现了一个患有GDAD的伊朗大家族。我们相信，对这一特殊病例的关注可能有助于国外临床医生识别这一诊断不足的实体。
Several genetic mutations are associated with nephrotic syndrome, including those of genes producing proteins nephrin, podocin, alpha actinin-4, an adapter protein anchoring CD-2, canonical transient receptor potential-6 and laminin beta-2 [1]. A G654A gelsolin gene mutation has also been found to be associated with severe nephrotic syndrome in homozygote patients [2]. Such a mutation results in the formation of a conformationally abnormal gelsolin protein [3, 4]. Impaired gelsolin function together with the generation of the amyloidogenic peptides by the cleavage of the mutant gelsolin causes a constellation of manifestations referred to as gelsolin-related amyloidosis, AGel amyloidosis or originally as familial amyloidosis, Finnish type [5]. The authors believe that referring to this disease as being solely an amyloidosis undermines some of its important pathogenic aspects. Because impaired gelsolin function is thought to play a critical role, even before amyloidogenesis, in the course of this disease, we used the term gelsolin dystrophy and amyloidosis disorder (GDAD) throughout this article. GDAD is an autosomal dominant systemic disorder with complete penetration, first described by Joko Meretoja in Finland in 1969 [6]. The cardinal clinical manifestations of GDAD are corneal lattice dystrophy, progressive cranial and peripheral neuropathy and cutis laxa, although every body organ could be affected [5–7]. Less frequent manifestations of this disease include, but are not limited to, macroglossia, endocrinopathies, osteoporosis, gait ataxia, autonomic dysfunction, cardiomyopathy, glucoma and cataract [5, 6]. Renal involvement is occasionally seen in GDAD, which usually manifests as intermittent proteinuria [6, 7]. The disease was first considered to be limited to Finland. However, several kindreds were later found in other parts of Europe; Denmark, the Netherlands, the former Czechoslovakia and the United States and Japan [5]. The large area between the Far East and Europe, Africa and South America had no record of GDAD.We report a patient with amyloidosis who presented with a nephrotic syndrome. Further investigations revealed a G654A gelsolin mutation and led to the discovery of a large Iranian family with GDAD. We believe that attention to this particular case may aid clinicians abroad in the identification of this under-diagnosed entity.