Biallelic Familial Hypercholesterolemia: Case study

Abstract

Abstract
Introduction – Familial hypercholesterolemia (FH) is a genetic lipoprotein metabolism disease with autosomal dominant inheritance. It
is characterised by very high levels of low-density lipoprotein cholesterol (LDL-c) in the blood and by the presence of clinical signs such
as tendon xanthomas, xanthelasmas, and corneal arcus. Vascular deposits promote progressive and premature atherosclerosis, with
consequent coronary artery disease and increased morbidity and mortality. Objective – to describe the cascade screening of a Brazilian
family of FH carriers. Material and methods – five members of a family, all of whom are patients followed by the paediatrics, medical
genetics, and cardiology department of the Magalhães Neto Outpatient Clinic of the Professor Edgard Santos University Hospital
(HUPES), answered questionnaires about clinical history and physical examination, medical history, family history, complementary
exams, and underwent genetic testing. Results – The index case presented two pathogenic variants in the LDLR gene: one pathogenic
variant, c.1118G>A, p. (Gly373Asp), in the LDLR gene, in heterozygosity, and the other pathogenic variant, c.1176C>A, p. (Cys392*),
in the LDLR gene, in heterozygosity. It also presented a variant of uncertain significance, c.12635C>G, p. (Thr4212Ser), in the APOB
gene, in heterozygosity. The mother of the index case presented a pathogenic variant c.1118G>A: p. (Gly373Asp), in the LDLR gene,
in heterozygosity; a pathogenic variant, c.796G>T: p. (Gly266*), in the LIPA gene, in heterozygosity; and a variant of uncertain
significance, c.12635C>G, p. (Thr4212Ser), in the APOB gene, in heterozygosity. Conclusion – The findings contributed to the clinical
and molecular diagnosis, treatment, and genetic counselling of a family with familial hypercholesterolemia.