Barbara Sjouke1, Joep C Defesche2, Janine S E de Randamie2, Albert Wiegman3, Sigrid W Fouchier4, G Kees Hovingh5. 1. Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: b.sjouke@amc.uva.nl. 2. Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands. 3. Department of Pediatrics, Academic Medical Center, Amsterdam, The Netherlands. 4. Department of Medical Biochemistry, Academic Medical Center, Amsterdam, The Netherlands. 5. Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Abstract
BACKGROUND AND AIMS: We recently identified lysosomal acid lipase (LAL) deficiency, a recessive disease caused by mutations in LIPA, in 3 patients with a clinical diagnosis of familial hypercholesterolemia (FH). We aimed to determine the prevalence of LIPA mutations among individuals with a clinical FH diagnosis. METHODS: In 276 patients with phenotypic FH, in whom no genetic basis for their phenotype was found, LIPA was sequenced. All variants were assessed for pathogenicity using a literature search and in silico prediction models. RESULTS: We included 213 adults and 63 children with mean (±SD) LDL-C levels of 7.8 ± 1.3 and 4.4 ± 1.5 mmol/L, respectively. Twenty-one variants were identified. Six patients were heterozygous carrier of a (potentially) pathogenic mutation. No homozygous LIPA mutation carriers were identified. CONCLUSIONS: Our data show that LAL deficiency was not missed as diagnosis in our study population but the frequency of heterozygous LIPA mutations implies that the FH population might be relatively enriched with LIPA mutation carriers.
BACKGROUND AND AIMS: We recently identified lysosomal acid lipase(LAL) deficiency, a recessive disease caused by mutations in LIPA, in 3 patients with a clinical diagnosis of familial hypercholesterolemia (FH). We aimed to determine the prevalence of LIPA mutations among individuals with a clinical FH diagnosis. METHODS: In 276 patients with phenotypic FH, in whom no genetic basis for their phenotype was found, LIPA was sequenced. All variants were assessed for pathogenicity using a literature search and in silico prediction models. RESULTS: We included 213 adults and 63 children with mean (±SD) LDL-C levels of 7.8 ± 1.3 and 4.4 ± 1.5 mmol/L, respectively. Twenty-one variants were identified. Six patients were heterozygous carrier of a (potentially) pathogenic mutation. No homozygous LIPA mutation carriers were identified. CONCLUSIONS: Our data show that LAL deficiency was not missed as diagnosis in our study population but the frequency of heterozygous LIPA mutations implies that the FH population might be relatively enriched with LIPA mutation carriers.
Authors: Natalia Loaiza; Merel L Hartgers; Aldo Grefhorst; Jan Albert Kuivenhoven; Laurens F Reeskamp; Jan-Willem Balder; Antoine Rimbert; Venetia Bazioti; Justina C Wolters; Maaike Winkelmeijer; Hans P G Jansen; Geesje M Dallinga-Thie; Andrea Volta; Nicolette Huijkman; Marieke Smit; Niels Kloosterhuis; Mirjam Koster; Arthur F Svendsen; Bart van de Sluis; G Kees Hovingh Journal: Arterioscler Thromb Vasc Biol Date: 2020-01-30 Impact factor: 8.311