Latkovskis Gustavs, Rescenko-Krums Raimonds, Nesterovics Georgijs, Briviba Monta, Saripo Vita, Gilis Dainus, Terauda Elizabete, Meiere Ruta, Skudrina Gunda, Erglis Andrejs, Chora Joana Rita, Bourbon Mafalda, Klovins Janis
Institute of Cardiology and Regenerative Medicine, University of Latvia, LV-1004 Riga, Latvia.
Latvian Center of Cardiology, Pauls Stradins Clinical University Hospital, LV-1002 Riga, Latvia.
J Clin Med. 2023 Aug 7;12(15):5160. doi: 10.3390/jcm12155160.
There is limited data on the genetic characteristics of patients with familial hypercholesterolemia (FH) in Latvia. We aim to describe monogenic variants in patients from the Latvian Registry of FH (LRFH).
Whole genome sequencing with 30× coverage was performed in unrelated index cases from the LRFH and the Genome Database of Latvian Population. , , , , , , , , , and genes were analyzed. Only variants annotated as pathogenic (P) or likely pathogenic (LP) using the FH Variant Curation Expert Panel guidelines for and adaptations for and were reported.
Among 163 patients, the mean highest documented LDL-cholesterol level was 7.47 ± 1.60 mmol/L, and 79.1% of patients had LDL-cholesterol ≥6.50 mmol/L. A total of 15 P/LP variants were found in 34 patients (diagnostic yield: 20.9%): 14 in the gene and 1 in the gene. Additionally, 24, 54, and 13 VUS were detected in and , respectively. No P/LP variants were identified in the other tested genes.
Despite the high clinical likelihood of FH, confirmed P/LP variants were detected in only 20.9% of patients in the Latvian cohort when assessed with genome-wide next generation sequencing.
拉脱维亚关于家族性高胆固醇血症（FH）患者遗传特征的数据有限。我们旨在描述拉脱维亚FH注册登记处（LRFH）患者中的单基因变异。
对来自LRFH和拉脱维亚人群基因组数据库的非亲缘索引病例进行了覆盖度为30×的全基因组测序。对 、 、 、 、 、 、 、 、 和 基因进行了分析。仅报告了根据FH变异整理专家小组指南针对 以及针对 和 的改编版本注释为致病性（P）或可能致病性（LP）的变异。
在163例患者中，记录到的最高LDL-胆固醇水平平均值为7.47±1.60 mmol/L，79.1%的患者LDL-胆固醇≥6.50 mmol/L。在34例患者中总共发现了15个P/LP变异（诊断率：20.9%）： 基因中有14个， 基因中有1个。此外，在 、 和 中分别检测到24个、54个和13个意义未明的变异（VUS）。在其他检测的基因中未鉴定出P/LP变异。
尽管FH的临床可能性很高，但在拉脱维亚队列中，通过全基因组下一代测序评估时，仅20.9%的患者检测到确诊的P/LP变异。
