由天冬酰胺或酪氨酸取代第187位残基上的天冬氨酸引起的凝溶胶蛋白源性家族性淀粉样变性。

Gelsolin-derived familial amyloidosis caused by asparagine or tyrosine substitution for aspartic acid at residue 187.

作者信息

de la Chapelle A, Tolvanen R, Boysen G, Santavy J, Bleeker-Wagemakers L, Maury C P, Kere J

机构信息

Department of Medical Genetics, University of Helsinki, Finland.

出版信息

Nat Genet. 1992 Oct;2(2):157-60. doi: 10.1038/ng1092-157.

DOI:10.1038/ng1092-157

PMID:1338910

Abstract

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.

摘要

显性遗传的芬兰型家族性淀粉样变性（FAF）是由突变型凝溶胶蛋白（GSN）的71个氨基酸的淀粉样生成片段积累所致。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族中，该突变是G654A转换，导致第187位残基处的天冬氨酸被天冬酰胺取代。我们在一个荷兰家族中发现了相同的突变，但一个丹麦FAF家族有G654T突变，预测第187位残基处的天冬氨酸被酪氨酸取代。我们还在一个捷克家族中发现了G654T颠换。利用GSN多态性，在丹麦和捷克家族中发现了不同的单倍型。我们得出结论，第187位残基处酸性的天冬氨酸被不带电荷的天冬酰胺或酪氨酸取代，会产生一种可能对GSN优先形成淀粉样蛋白的构象。