PDF(Pubmed)
Abstract：
UNASSIGNED: Hereditary thrombotic thrombocytopenic purpura (hTTP) is a rare autosomal recessive, life-threatening disorder caused by a severe deficiency of the plasma enzyme, ADAMTS13. The current estimated prevalence of hTTP in different regions of the world, 0.5 to 2.0 patients per million, is determined by the frequency of diagnosed patients. To evaluate more accurately the worldwide prevalence of hTTP, and also the prevalence within distinct ethnic groups, we used data available in exome and genome sequencing of 807 162 (730 947 exomes, 76 215 genomes) subjects reported recently by the Genome Aggregation Database (gnomAD-v4.1). Among 1 614 324 analyzed alleles in the gnomAD population we identified 6321 distinct ADAMTS13 variants. Of these, 758 were defined as pathogenic; 140 (18%) variants had been previously reported and 618 (82%) were novel (predicted as pathogenic). In total 10 154 alleles (0.6%) were carrying the reported or predicted pathogenic variants; 7759 (77%) with previously reported variants. Considering all 758 pathogenic variants and also only the 140 previously reported variants, we estimated a global hTTP prevalence of 40 and 23 cases per 106, respectively. Considering only the 140 previously reported variants, the highest estimated prevalence was in East Asians (42 per 106). The estimated prevalences of other populations were: Finnish, 32 per 106; non-Finnish Europeans, 28 per 106; Admixed Americans, 19 per 106; Africans/African Americans, 6 per 106; and South Asians, 4 per 106. The lowest prevalences were Middle Eastern, 1 per 106 and Ashkenazi Jews, 0.7 per 106. This population-based genetic epidemiology study reports that hTTP prevalence is substantially higher than the currently estimated prevalence based on diagnosed patients. Many patients with hTTP may not be diagnosed or may have died during the neonatal period.
摘要：
遗传性血栓性血小板减少性紫癜（hTTP）是一种罕见的常染色体隐性遗传，由血浆酶严重缺乏引起的危及生命的疾病，ADAMTS13.目前估计世界不同地区的hTTP患病率，0.5-2.0患者/百万，由确诊患者的频率决定。为了更准确地评估hTTP的全球患病率，以及不同种族群体中的患病率，我们使用外显子组和基因组测序中可用的数据，对807,162(730,947个外显子组，基因组聚集数据库（gnomAD-v4.1）最近报告的76,215个基因组）受试者。在gnomAD群体中的1,614,324个分析等位基因中，我们鉴定了6,321个不同的ADAMTS13变体。在这些6,321种变体中，758个被定义为致病性;140（18％）的变体以前已经报道和618（82％）是新的（预测为致病性）。10,154个等位基因（0.6％）携带报告或预测的致病变异；7,759个（77％）具有先前报告的变异。考虑到所有758个致病变异，也只有140个以前报道的变异，我们估计全球hTTP患病率分别为40例和23例/106例.仅考虑先前报道的140种变体，估计患病率最高的是东亚人(42/106).其他人群的估计患病率为：芬兰语，32/106；非芬兰欧洲人，28/106；混合美国人，19/106；非洲人/非裔美国人，6/106；和南亚人，4/106.流行率最低的是中东，1/106和阿什肯纳齐犹太人，0.7/106.这项基于人群的遗传流行病学研究报告，hTTP患病率大大高于目前基于诊断患者的估计患病率。许多hTTP患者可能未被诊断或可能在新生儿期死亡。
