Independent Medico-Diagnostic Laboratory Genome Center "Bulgaria", Sofia, Bulgaria.
Genetic Medico-Diagnostic Laboratory Genica, Sofia, Bulgaria.
Amyloid. 2021 Dec;28(4):219-225. doi: 10.1080/13506129.2021.1935230. Epub 2021 Jun 2.
The hereditary transthyretin amyloidosis (ATTRv amyloidosis) is an autosomal dominant genetic disease characterized by amyloid formation in different tissues due to pathogenic variants in the gene. Great heterogeneity in the penetrance and manifestation of ATTRv amyloidosis is observed. In Bulgaria, the most common pathogenic variant is . Other pathogenic variants are also found - and . There is a proven founder effect for the variant, thus the aim of the present study is to investigate the founder effect for the other pathogenic variants in Bulgaria. Haplotype analysis was performed by using microsatellite markers close to the gene. DNA samples from ATTRv amyloidosis patients and their healthy relatives were analyzed. Theoretical haplotype reconstruction was done with Arlequin v.3.01 software. The age of the most recent common ancestor (hypothetical founder) for the studied variants was calculated with the DMLE 2.2 software. In addition, DBS screening among 100 Roma newborns was done for the variant via direct Sanger sequencing. The reconstructed haplotypes of the patients were compared to their healthy relatives and to a control group of 40 healthy individuals. The results showed a possible founder effect for each of the studied variants. The haplotype was compared to published haplotype data for this variant and no similarity was found. The result from the DBS screening showed no pathogenic variants in exon 2 of the gene, so we considered the presence of the variant in our population a sporadic event. With this study, we succeeded to gain a more complete picture of the population genetics of ATTRv amyloidosis in Bulgaria and made another step towards a more detailed understanding of the disease epidemiology.
遗传性转甲状腺素淀粉样变性（ATTRv 淀粉样变性）是一种常染色体显性遗传疾病，其特征是由于 基因中的致病变体导致不同组织中的淀粉样形成。ATTRv 淀粉样变性的外显率和表现度存在很大的异质性。在保加利亚，最常见的致病变体是 。还发现了其他致病变体- 和 。对于 变体存在已证实的创始人效应，因此本研究旨在调查保加利亚其他致病变体的创始人效应。使用靠近 基因的微卫星标记进行单体型分析。分析 ATTRv 淀粉样变性患者及其健康亲属的 DNA 样本。使用 Arlequin v.3.01 软件进行理论单体型重建。使用 DMLE 2.2 软件计算研究变体的最近共同祖先（假设创始人）的年龄。此外，通过直接 Sanger 测序对 100 名罗姆新生儿进行了 变体的 DBS 筛查。将患者的重建单体型与其健康亲属和 40 名健康个体的对照组进行比较。结果表明，每个研究变体都存在可能的创始人效应。与该变体的已发表单体型数据相比， 单体型没有相似性。DBS 筛查结果显示该基因外显子 2 中没有致病性 变体，因此我们认为该人群中 变体的存在是偶发事件。通过这项研究，我们成功地获得了保加利亚 ATTRv 淀粉样变性人群遗传学的更完整图像，并朝着更详细地了解疾病流行病学迈出了一步。
