title: Homozygous Familial Hypercholesterolemia in Spain: Prevalence and Phenotype-Genotype Relationship.
abstract: BACKGROUND
  Homozygous familial hypercholesterolemia (HoFH) is a rare disease characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) and extremely high risk of premature atherosclerotic cardiovascular disease. HoFH is caused by mutations in several genes, including LDL receptor (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin/kexin type 9 (PCSK9), and LDL protein receptor adaptor 1 (LDLRAP1). No epidemiological studies have assessed HoFH prevalence or the clinical and molecular characteristics of this condition. Here, we aimed to characterize HoFH in Spain.
  
  
  RESULTS
  Data were collected from the Spanish Dyslipidemia Registry of the Spanish Atherosclerosis Society and from all molecular diagnoses performed for familial hypercholesterolemia in Spain between 1996 and 2015 (n=16 751). Clinical data included baseline lipid levels and atherosclerotic cardiovascular disease events. A total of 97 subjects were identified as having HoFH-of whom, 47 were true homozygous (1 for APOB, 5 for LDLRAP1, and 41 for LDLR), 45 compound heterozygous for LDLR, 3 double heterozygous for LDLR and PSCK9, and 2 double heterozygous for LDLR and APOB. No PSCK9 homozygous cases were identified. Two variants in LDLR were identified in 4.8% of the molecular studies. Over 50% of patients did not meet the classical HoFH diagnosis criteria. The estimated HoFH prevalence was 1:450 000. Compared with compound heterozygous cases, true homozygous cases showed more aggressive phenotypes with higher LDL-C and more atherosclerotic cardiovascular disease events.
  
  
  CONCLUSIONS
  HoFH frequency in Spain was higher than expected. Clinical criteria would underestimate the actual prevalence of individuals with genetic HoFH, highlighting the importance of genetic analysis to improve familial hypercholesterolemia diagnosis accuracy.
authors: Rosa M
authors: RM
authors: Sánchez-Hernández
authors: Fernando
authors: F
authors: Civeira
authors: Marianne
authors: M
authors: Stef
authors: Sofía
authors: S
authors: Perez-Calahorra
authors: Fátima
authors: F
authors: Almagro
authors: Nuria
authors: N
authors: Plana
authors: Francisco J
authors: FJ
authors: Novoa
authors: Pedro
authors: P
authors: Sáenz-Aranzubía
authors: Daniel
authors: D
authors: Mosquera
authors: Cristina
authors: C
authors: Soler
authors: Francisco J
authors: FJ
authors: Fuentes
authors: Yeray
authors: Y
authors: Brito-Casillas
authors: Jose T
authors: JT
authors: Real
authors: Francisco
authors: F
authors: Blanco-Vaca
authors: Juan F
authors: JF
authors: Ascaso
authors: Miguel
authors: M
authors: Pocovi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000293:Adolescent; D000328:Adult; D053299:Apolipoprotein B-100 / Q000235:genetics; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics; D008078:Cholesterol, LDL / Q000097:blood*; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D009154:Mutation; D010641:Phenotype; D015995:Prevalence; D000071449:Proprotein Convertase 9 / Q000235:genetics; D011973:Receptors, LDL / Q000235:genetics; D012042:Registries; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology; D055815:Young Adult
chemical_list: C569471:APOB protein, human; D048868:Adaptor Proteins, Signal Transducing; D053299:Apolipoprotein B-100; D008078:Cholesterol, LDL; D005819:Genetic Markers; C573412:LDLR protein, human; C469745:LDLRAP1 protein, human; D011973:Receptors, LDL; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9
keywords: alleles; hypercholesterolemia; lipids; mutation; registries