AUTHOR=Blokhina Anastasia V. , Ershova Alexandra I. , Meshkov Alexey N. , Kiseleva Anna V. , Klimushina Marina V. , Zharikova Anastasia A. , Sotnikova Evgeniia A. , Ramensky Vasily E. , Drapkina Oxana M. 

TITLE=Phenotypic vs. genetic cascade screening for familial hypercholesterolemia: A case report

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.982607

DOI=10.3389/fcvm.2022.982607

ISSN=2297-055X

ABSTRACT=One of the most common autosomal dominant disorder is familial hypercholesterolemia (FH), causing premature atherosclerotic cardiovascular diseases and a high risk of death due to the lifelong exposure to elevated low-density lipoprotein cholesterol (LDL-C) levels. FH has a proven arsenal of treatments and the opportunity of genetic diagnosis. Despite this, FH remains largely underdiagnosed worldwide. Cascade screening is a cost-effective method for the identification of new FH patients and prevention of cardiovascular diseases. It`s usually based only on clinical data. We describe a 48-year-old index patient with a very high LDL-C level without controlled guidelines-based medication, premature atherosclerosis and with a rare variant in low-density lipoprotein receptor (LDLR) gene. Phenotypic cascade screening identified three additional FH relatives, namely proband’s daughter and two young grandsons. The genetic screening made it possible to rule out FH in the proband’s younger grandson. This clinical case demonstrates the genetic cascade screening as the most effective way for identifying new FH cases. We also first described in detail the phenotype of patients with a likely pathogenic variant LDLR-p.K223_D227dup.