Sequencing for LIPA mutations in patients with a clinical diagnosis of familial hypercholesterolemia. (August 2016)

• Record Type: Journal Article
• Authors: Sjouke, Barbara; Defesche, Joep C.; de Randamie, Janine S.E.; Wiegman, Albert; Fouchier, Sigrid W.; Hovingh, G. Kees
• Is Part Of: Atherosclerosis. Volume 251(2016)
• Page Start: 263
• Page End: 265
• Publication Date: 2016-08
• Subjects: LAL deficiency -- LIPA -- Familial hypercholesterolemia -- Cholesteryl ester storage disease; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2016.07.008
• Languages: English
• ISSNs: 0021-9150

Abstract

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. Highlights: We studied the prevalence of LIPA mutations among clinically diagnosed FH patients. From 276 patients, six were heterozygous for a (potentially) pathogenic mutation. No homozygous LIPA mutation carriers were identified. LAL deficiency was not missed as diagnosis in our study population. The FH population might be relatively enriched with LIPA mutation carriers.