title: Sequencing for LIPA mutations in patients with a clinical diagnosis of familial hypercholesterolemia.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: b.sjouke@amc.uva.nl.
authors.forename: Barbara
authors.initials: B
authors.lastname: Sjouke
authors.affiliation: Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Joep C
authors.initials: JC
authors.lastname: Defesche
authors.affiliation: Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Janine S E
authors.initials: JSE
authors.lastname: de Randamie
authors.affiliation: Department of Pediatrics, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Wiegman
authors.affiliation: Department of Medical Biochemistry, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Sigrid W
authors.initials: SW
authors.lastname: Fouchier
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: G Kees
authors.initials: GK
authors.lastname: Hovingh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D015995:Prevalence; D002787:Sterol Esterase / Q000235:genetics*; D014280:Triglycerides / Q000097:blood; D015223:Wolman Disease / Q000235:genetics*
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides; C503451:LIPA protein, human; D002787:Sterol Esterase
keywords: Cholesteryl ester storage disease; Familial hypercholesterolemia; LAL deficiency; LIPA