A case report of hereditary apolipoprotein A-I amyloidosis associated with a novel APOA1 mutation and variable phenotype
A case report of hereditary apolipoprotein A-I amyloidosis associated with a novel APOA1 mutation and variable phenotype
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DOI：
10.1016/j.ejmg.2016.05.015
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发表时间：
2016-09-01
影响因子：
1.9
通讯作者：
Birn, Henrik
中科院分区：
文献类型：
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作者：
Tougaard, Birgitte G.;Pedersen, Katja Venborg;Birn, Henrik
载脂蛋白A-I（apo A-I）淀粉样变性是一种非AL、非AA和非甲状腺素运载蛋白类型的淀粉样变性，与以常染色体显性遗传方式遗传的APOA 1基因突变相关。它是系统性淀粉样变性的一种形式，但在临床表现上，也可以模仿局部淀粉样变性。肾脏表现通常包括间质和髓质的apoA-I淀粉样蛋白沉积.我们描述了在一名52岁男性患者中通过质谱鉴定载脂蛋白A-I淀粉样变性，该患者无淀粉样变性家族史，表现为肾病综合征，并与编码已知淀粉样蛋白Trp 50 Arg变体的新型APOA 1突变（c.220 T > A）的杂合性相关。在这个病例中，肾淀粉样蛋白沉积仅限于肾小球，并且患者发展为进行性肾损害。确诊一年后，患者成功接受了来自无关供体的肾移植。APOA 1基因的致病性突变通常与淀粉样变性的症状相关。然而，在这个家族中，家族成员的基因分型鉴定出几个未受影响的携带者，这表明可变的疾病突变率，这在这种淀粉样变性中以前没有描述过，并且在咨询APOA 1突变的患者时有意义。(C)2016 Elsevier Masson SAS。All rights reserved.
Apolipoprotein A-I (apo A-I) amyloidosis is a non-AL, non-AA, and non-transthyretin type of amyloidosis associated with mutations in the APOA1 gene inherited in an autosomal dominant fashion. It is a form of systemic amyloidosis, but at presentation, can also mimic localized amyloidosis. The renal presentation generally involves interstitial and medullary deposition of apo A- I amyloid protein. We describe the identification of apo A- I amyloidosis by mass spectrometry in a 52-year old male, with no family history of amyloidosis, presenting with nephrotic syndrome and associated with heterozygosity for a novel APOA1 mutation (c.220 T > A) which encodes the known amyloidogenic Trp50Arg variant. Renal amyloid deposits in this case were confined to the glomeruli alone, and the patient developed progressive renal impairment. One year after diagnosis, the patient had a successful kidney transplant from an unrelated donor. Pathogenic mutations in the APOA1 gene are generally associated with symptoms of amyloidosis. In this family however, genotyping of family members identified several unaffected carriers suggesting a variable disease penetrance, which has not been described before in this form of amyloidosis and has implications when counselling those with APOA1 mutations. (C) 2016 Elsevier Masson SAS. All rights reserved.