Clinical features and haplotype analysis of newly identified Japanese patients with gelsolin-related familial amyloidosis of Finnish type
Clinical features and haplotype analysis of newly identified Japanese patients with gelsolin-related familial amyloidosis of Finnish type
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DOI：
10.1007/s10048-012-0330-0
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发表时间：
2012-08-01
期刊：
影响因子：
2.2
通讯作者：
Tsuji, Shoji
中科院分区：
文献类型：
--
作者：
Taira, Makiko;Ishiura, Hiroyuki;Tsuji, Shoji
芬兰型家族性淀粉样变性（FAF）是系统性淀粉样变性的常染色体显性遗传形式，其特征为格子状角膜营养不良、颅神经病变和皮肤松弛。尽管 FAF 在芬兰人群中很常见，但 FAF 在其他地区是一种相当罕见的疾病。在这项研究中，我们检查了来自 5 个家庭的 6 名日本 FAF 患者的临床特征和单倍型。他们表现出 FAF 的典型临床表现，但我们发现神经系统症状出现的年龄范围很广。所有成员的 GSN 均具有 c.654G > A 突变。为了评估疾病单倍型，使用高密度单核苷酸多态性（SNP）阵列并重建与疾病相关的单倍型。对四个明显不相关的家族进行的单倍型分析表明有一个共同的创始人单倍型。然而，在散发性 FAF 患者中，单倍型与创始人单倍型不同。目前的研究表明，大多数患有 FAF 的日本家庭都存在创始人突变，除了一名零星患者外，该患者中的新生突变事件被认为是突变的起源。
Familial amyloidosis of the Finnish type (FAF) is an autosomal dominant form of systematic amyloidosis characterized by lattice corneal dystrophy, cranial neuropathy, and cutis laxa. Although FAF has been frequently found in the Finnish population, FAF is a considerably rare disorder in other regions. In this study, we examined the clinical characteristics as well as the haplotypes of six Japanese patients with FAF from five families. They showed the typical clinical presentations of FAF, but we found a broad range of ages at onset of neurological symptoms. All members had the c.654G > A mutation in GSN. To evaluate the disease haplotypes, high-density single-nucleotide polymorphism (SNP) arrays were used and disease-relevant haplotypes were reconstructed. Haplotype analysis in the four apparently unrelated families suggested a common founder haplotype. In a sporadic FAF patient, however, the haplotype was dissimilar to the founder haplotype. The present study demonstrated that a founder mutation in most of the Japanese families with FAF, except for a sporadic patient in whom a de novo mutation event was suggested as the origin of the mutation.