Genetic and Clinical Characteristics of Patients With Homozygous and Compound Heterozygous Familial Hypercholesterolemia From Three Different Populations: Case Series

Marusic, Tatiana and Sustar, Ursa and Sadiq, Fouzia and Kotori, Vjosa and Mlinaric, Matej and Kovac, Jernej and Shafi, Saeed and Khan, Iqbal and Cevc, Matija and Trebusak Podkrajsek, Katarina and Battelino, Tadej and Groselj, Urh (2020) Genetic and Clinical Characteristics of Patients With Homozygous and Compound Heterozygous Familial Hypercholesterolemia From Three Different Populations: Case Series. Frontiers in Genetics, 11. ISSN 1664-8021

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Abstract

Homozygous familial hypercholesterolemia (HoFH) and compound heterozygous familial hypercholesterolemia (cHeFH) are rare disorders generated by disease-causing variants in both alleles of the LDLR or other familial hypercholesterolemia (FH)-related genes. HoFH and cHeFH are characterized by severely elevated low-density lipoprotein-cholesterol (LDL-C), frequently leading to early cardiovascular disease. We investigated the genetic and clinical characteristics of HoFH and cHeFH patients from the Slovenian FH registry and/or those who were previously diagnosed or managed at our institution (Slovenian, Pakhtun and Albanian ethnicity), where genetic testing is not available. Our study includes seven patients. Their median age at the time of clinical diagnosis was 6.3 years (2.9–12.9 years); 2/7 were females. Two patients were diagnosed through the universal FH screening and five patients were diagnosed due to the presence of xanthomas. All the mutations are present in LDLR gene: 7 different genotypes for HoFH (p.Cys167Leu, p.Asp178Asn, p.Cys243Tyr, p.Gly549Asp, p.Cys27Trp, p.Ile585Thr and p.Val797Met) and p.Gly549Asp/p.Gln384Pro genotype for cHeFH patient. The median initial level of LDL-C was 17.0 mmol/L [655 mg/dL] (range 7.6–21.6 mmol/L). The HoFH/cHeFH patients are clinically and genetically very diverse. The clinical criteria (as Simon Broome criteria) might be applicable already in children to raise suspicion of FH but in some cases fail to distinguish heterozygous FH and HoFH/cHeFH patients. However, genetic testing is helpful in confirming the diagnosis, also for a prompt awareness, better compliance to treatment and family screening.

Item Type: Article
Subjects: Research Scholar Guardian > Medical Science
Depositing User: Unnamed user with email support@scholarguardian.com
Date Deposited: 07 Feb 2023 13:03
Last Modified: 03 Jan 2024 06:30
URI: http://science.sdpublishers.org/id/eprint/143

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