Hereditary transthyretin amyloidosis is an autosomal dominant genetic disorder caused by missense mutations in the TTR gene resulting in amyloid formation of the transthyretin protein. Depending on the system affection, the manifestations may be different and high heterogeneity in the penetrance is observed. An endemic region in Bulgaria exists where the TTR mutation Glu89Gln is found with high frequency. This is a rare mutation and was probably introduced in the population by a common ancestor. This phenomenon, called “founder effect” was proved in carrier families by haplotype analysis of microsatellite markers showing linkage disequilibrium. Allele frequencies were analyzed and haplotype reconstruction was done with Arlequin v.3.01 software. The common ancestry of the carriers was demonstrated using additional data for their genealogies and microsatellite data from a control group of non-affected individuals. The results show that the mutation Glu89Gln is linked to one haplotype, called “hypothetical founder haplotype” which was compared to published haplotype data from other European patients and no similarity was found. Further population genetics studies of carriers of the Glu89Gln mutation from other endemic regions are required in order to clarify the geographical distribution of the mutation.

遗传性运甲状腺素蛋白淀粉样变性是一种常染色体显性遗传疾病，由TTR基因的错义突变引起，导致运甲状腺素蛋白蛋白的淀粉样蛋白形成。取决于系统的影响，表现形式可能会有所不同，并且会观察到外et现象的高度异质性。保加利亚存在TTR的地方病区发现Glu89Gln突变频率很高。这是罕见的突变，很可能是由共同祖先引入种群中的。通过对显示连锁不平衡的微卫星标记进行单倍型分析，在载体家族中证明了这种称为“基础效应”的现象。分析等位基因频率，并使用Arlequin v.3.01软件完成单倍型重建。通过使用家谱的其他数据和来自未受影响个体对照组的微卫星数据，证明了携带者的共同血统。结果表明，Glu89Gln突变与一种单体型有关，该单体型称为“假设的创始人单体型”，该单体型与来自其他欧洲患者的已公布单体型数据进行了比较，但未发现相似性。