RARE TRANSTHYRETIN MUTATION (ASP18GLU) ASSOCIATED WITH CARDIOMYOPATHY

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。一个罕见的甲状腺素运载蛋白（TTR）基因突变（Asp 18 Glu）的中年男性活检证实淀粉样疾病的特点是心肌病的鉴定。更常见的轻链淀粉样变性（AL）最初被认为是，但阴性血液学检测提示筛查病理TTR突变。采用分子遗传学和生物化学技术相结合的方法建立了家族性甲状腺素运载蛋白型淀粉样变性（ATTR）的鉴别诊断。TTR基因第2、3、4外显子的单链构象多态性（SSCP）分析表明存在非典型DNA。使用新的非放射性、银染微型凝胶技术进行SSCP检测。通过直接DNA序列分析确定遗传异常为密码子18中第三个碱基位置的T至A颠换。这一结果得到了限制性片段长度多态性（RFLP）测试的证实。在BUSM MS Resource通过质谱分析证实了先证者血清中存在变异蛋白TTR Asp 18 Glu。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The identification of a rare transthyretin (TTR) gene mutation (Asp18Glu) in a middle-aged male with biopsy proven amyloid disease featuring cardiomyopathy was achieved. The more commonly occurring light chain amyloidosis (AL) was initially considered, but negative hematologic testing prompted screening for a pathologic TTR mutation. A differential diagnosis of familial transthyretin type amyloidosis (ATTR) was established using a combination of molecular genetic and biochemical techniques. Single-strand conformation polymorphism (SSCP) screening of exons 2, 3 and 4 of the TTR gene indicated the presence of atypical DNA. SSCP testing was performed using a new non-radioactive, silver stained minigel technique. The genetic abnormality was identified by direct DNA sequence analysis as a T to A transversion at the third base position in codon 18. This result was confirmed by restriction fragment length polymorphism (RFLP) testing. The presence of the variant protein, TTR Asp18Glu, in serum from the proband was confirmed by mass spectrometric analysis at the BUSM MS Resource.