A novel lysozyme mutation Phe57Ile associated with hereditary renal amyloidosis.
A novel lysozyme mutation Phe57Ile associated with hereditary renal amyloidosis.
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DOI：
10.1046/j.1523-1755.2003.00904.x
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发表时间：
2003-05
影响因子：
19.6
通讯作者：
M. Yazaki;S. Farrell;M. Benson
中科院分区：
文献类型：
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作者：
M. Yazaki;S. Farrell;M. Benson
背景技术溶菌酶是一种普遍存在的溶菌酶，已知其变异形式可导致遗传性非神经性肾淀粉样变性，迄今为止，已报道了溶菌酶基因的三种不同突变。在这项研究中，我们报告了一种新的溶菌酶变异体，Phe57Ile，与肾淀粉样变性在一个意大利裔加拿大家庭的三名患者。方法先证者是一名52岁的女性，在42岁时出现肾功能衰竭。肾活检显示肾小球被淀粉样蛋白替代。她的妹妹和接受肾移植的小女儿也患有肾淀粉样变性。先证者的大女儿和侄女身体健康。为了阐明这种遗传性肾淀粉样变性的发病机制，溶菌酶基因的DNA分析，包括单链确认多态性，直接DNA序列，和限制性片段长度多态性分析，进行。结果先证者、其姐妹、患病和未患病的女儿的溶菌酶基因第57位密码子第一位T → A颠换，表明第57位残基Phe被Ile取代。此外，DNA测序显示，在第二位的密码子70的C到A颠换，表示由Asn在残基70，先证者的妹妹和她的侄女的Thr的替代。因此，先证者的姐姐是Phe57Ile和Thr70Asn等位基因的复合杂合子。结论该家系以肾淀粉样变肾病为主要临床特征。我们的研究结果表明，新的溶菌酶变体Phe57Ile与肾淀粉样变性在这个家庭。从我们的结果来看，Thr70Asn多态性与肾淀粉样变之间的关系尚不明确。
BACKGROUND Variant forms of lysozyme, a ubiquitous bacteriolytic enzyme, are known to lead to hereditary non-neuropathic renal amyloidosis and, so far, three different mutations of the lysozyme gene have been reported. In this study, we report a novel lysozyme variant, Phe57Ile, associated with renal amyloidosis in three patients in one Italian Canadian family. METHODS The proband was a 52-year-old woman who developed renal failure at the age of 42 years. Renal biopsy demonstrated replacement of glomeruli by amyloid. Her younger sister and her younger daughter who underwent renal transplantation also had renal amyloidosis. The proband's older daughter and her niece were in good health. To elucidate pathogenesis of this hereditary renal amyloidosis, DNA analyses of the lysozyme gene, including single strand confirmation polymorphism, direct DNA sequence, and restriction fragment length polymorphism analyses, were performed. RESULTS DNA analyses of the lysozyme gene revealed a T to A transversion at the first position of codon 57 of the lysozyme gene in the proband, her sister, and her affected and unaffected daughters, indicating a replacement of Phe by Ile at residue 57. In addition, DNA sequencing demonstrated a C to A transversion at the second position of codon 70, denoting a replacement of Thr by Asn at residue 70, in the proband's sister and her niece. Thus, the proband's sister is compound heterozygous for the Phe57Ile and Thr70Asn alleles. CONCLUSION Distinctive clinical features in patients of this family are nephropathy due to renal amyloidosis. Our results indicate that the novel lysozyme variant Phe57Ile is associated with renal amyloidosis in this family. From our results, a clear relation between the Thr70Asn polymorphism and renal amyloidosis could not be demonstrated.