Renal Amyloidosis Associated With a Novel Sequence Variant of Gelsolin
Renal Amyloidosis Associated With a Novel Sequence Variant of Gelsolin
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DOI：
10.1053/j.ajkd.2012.07.016
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发表时间：
2013-01-01
影响因子：
13.2
通讯作者：
Highsmith, Edward W., Jr.
中科院分区：
文献类型：
--
作者：
Sethi, Sanjeev;Theis, Jason D.;Highsmith, Edward W., Jr.
我们报告一位75岁的女性，以进行性肾衰竭来表现。为确定肾衰竭原因而进行的肾活检显示类型不明的淀粉样变性。激光显微切割刚果红阳性肾小球，随后进行质谱研究，结果显示大量光谱与载脂蛋白E、血清淀粉样蛋白P组分和凝溶胶蛋白相匹配，与凝溶胶蛋白相关性肾淀粉样变性的诊断一致。凝溶胶蛋白基因的测序揭示了一个先前未描述的序列变体，在编码序列的核苷酸580处鸟嘌呤变为腺嘌呤，对应于预测的氨基酸194处甘氨酸变为精氨酸的突变。凝溶胶蛋白淀粉样变性通常累及神经和皮肤，仅罕见报道累及肾脏。电子显微镜下的一个非典型发现是淀粉样纤维的漩涡图案。新的凝溶胶蛋白变异体可能是不寻常的临床和病理表现。该报告还强调了激光显微切割和质谱在淀粉样变性疑难病例分型中的作用。美国肾脏病杂志61（1）：161-166。(C)2012年，美国国家肾脏基金会（National Kidney Foundation，Inc.）
We present a case of a 75-year-old woman who presented with progressive kidney failure. Kidney biopsy performed to determine the cause of kidney failure showed amyloidosis of undetermined type. Laser microdissection of the Congo Red-positive glomeruli followed by mass spectrometry studies showed a large number of spectra matching apolipoprotein E, serum amyloid P component, and gelsolin, consistent with a diagnosis of gelsolin-associated renal amyloidosis. Sequencing of the gelsolin gene revealed a previously undescribed sequence variant, a guanine to adenine substitution at nucleotide 580 of the coding sequence, corresponding to a predicted glycine to arginine mutation at amino acid 194. Gelsolin amyloidosis typically involves the nerves and skin, with only rare reported involvement of the kidney. An atypical finding on electron microscopy was that of a swirling pattern of the amyloid fibrils. The novel gelsolin variant may be responsible for the unusual clinical and pathologic presentation. The report also highlights the usefulness of laser microdissection and mass spectrometry in the typing of difficult cases of amyloidosis. Am J Kidney Dis. 61(1):161-166. (C) 2012 by the National Kidney Foundation, Inc.