Gelsolin gene mutation--at codon 187--in familial amyloidosis, Finnish: DNA-diagnostic assay.
Gelsolin gene mutation--at codon 187--in familial amyloidosis, Finnish: DNA-diagnostic assay.
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家族性淀粉样变性中的凝溶胶蛋白基因突变（密码子 187），芬兰语：DNA 诊断测定。
DOI：
10.1002/ajmg.1320420321
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Frangione,B
中科院分区：
文献类型：
--
作者：
Haltia,M;Levy,E;Meretoja,J;Fernandez-Madrid,I;Koivunen,O;Frangione,B
芬兰家族性淀粉样变性（FAF）是一种常染色体显性遗传的系统性淀粉样变性，主要临床表现为格子状角膜营养不良和进行性颅神经病变。我们已经证明，在这些患者中发现的新型淀粉样原纤维蛋白是凝溶胶蛋白（一种肌动蛋白结合蛋白）的内部降解片段，并且它包含氨基酸取代，在位置15处天冬氨酸被天冬酰胺取代，这是由于对应于人血浆凝溶胶蛋白cDNA密码子187的鸟嘌呤至腺嘌呤颠换。为了测试该突变与疾病共分离，从23名患者、6名健康亲属和20名无关健康对照者的尸检组织或淋巴细胞中分离高分子量基因组DNA。采用聚合酶链反应扩增特异性片段，采用狭缝印迹技术进行寡核苷酸杂交分析。在所有受试FAF患者中均发现鸟嘌呤至腺嘌呤颠换，但在对照受试者中均未发现。我们的结果表明，突变（G到A）与疾病表型共分离，并且狭缝印迹分析可用作诊断测定，包括产前评估。
Familial amyloidosis, Finnish (FAF), is an autosomal dominant form of systemic amyloidosis with lattice corneal dystrophy and progressive cranial neuropathy as principal clinical manifestations. We have shown that the novel amyloid fibril protein found in these patients is an internal degradation fragment of gelsolin, an actin‐binding protein, and that it contains an amino acid substitution, asparagine for aspartic acid at position 15, that is due to a guanine‐to‐adenine transversion corresponding to codon 187 of human plasma gelsolin cDNA. To test that this mutation cosegregates with the disease high‐molecular‐weight genomic DNA was isolated from autopsied tissues or lymphocytes of 23 patients, 6 healthy relatives and 20 unrelated healthy control persons. Specific fragments were amplified with the polymerase chain reaction for oligonucleotide hybridization analysis using the slot‐blot technique. The guanine‐to‐adenine transversion was found in all FAF patients tested, but in none of the control subjects. Our results show that the mutation (G to A) cosegregates with the disease phenotype, and that the slot‐blot analysis can be used as a diagnostic assay, including prenatal evaluation.