GELSOLIN-DERIVED FAMILIAL AMYLOIDOSIS CAUSED BY ASPARAGINE OR TYROSINE SUBSTITUTION FOR ASPARTIC-ACID AT RESIDUE 187
GELSOLIN-DERIVED FAMILIAL AMYLOIDOSIS CAUSED BY ASPARAGINE OR TYROSINE SUBSTITUTION FOR ASPARTIC-ACID AT RESIDUE 187
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DOI：
10.1038/ng1092-157
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发表时间：
1992-10-01
期刊：
影响因子：
30.8
通讯作者：
KERE, J
中科院分区：
文献类型：
--
作者：
DELACHAPELLE, A;TOLVANEN, R;KERE, J
芬兰型家族性淀粉样变性(FAF)是由突变明胶蛋白(GSN)的71个氨基酸组成的淀粉样变性片段积聚引起的。FAF在芬兰很常见，但在其他地方非常罕见。在芬兰和两个美国家庭中，突变是G654A转换，导致第187位天冬氨酸到天冬氨酸的替换。我们在一个荷兰家庭中发现了同样的突变，但在一个丹麦Faf家庭中发现了G654T突变，预测Asp到Tyr的残基为187。我们还在一个捷克家庭中发现了G654T易位。利用GSN基因多态性分析，发现丹麦和捷克家系中存在不同的单倍型。我们得出结论，在第187位氨基酸残基上，不带电荷的Asn或Tyr取代酸性Asp产生了一种构象，该构象可能优先导致GSN的淀粉样变性。
Dominantly inherited familial amyloidosis, Finnish type (FAF) is caused by the accumulation of a 71-amino acid amyloidogenic fragment of mutant gelsolin (GSN). FAF is common in Finland but is very rare elsewhere. In Finland and in two American families, the mutation is a G654A transition leading to an Asp to Asn substitution at residue 187. We found the same mutation in a Dutch family but a Danish FAF family had a G654T mutation, predicting Asp to Tyr at residue 187. We also found the G654T transversion in a Czech family. Using GSN polymorphisms, different haplotypes were found in the Danish and Czech families. We conclude that substitution of the uncharged Asn or Tyr for the acidic Asp at residue 187 creates a conformation that may be preferentially amyloidogenic for GSN.