title: Familial hypobetalipoproteinemia: analysis of three Spanish cases with two new mutations in the APOB gene.
abstract: Extremely low LDL-cholesterol concentrations are very unusual and generally related with comorbidities accompanying malnutrition. Less frequently low LDL-cholesterol levels result from mutations in the APOB, PCSK9, ANGPTL3, SAR1B and MTTP genes (primary hypobetalipoproteinemia). We investigated three patients with plasma LDL-cholesterol levels below the fifth percentile of the Spanish population. We recorded data on demographic and anthropometric characteristics, life style habits, physical examination, liver ultrasound and lipid and lipoprotein levels, in the probands and their first-degree relatives. Secondary causes of hypocholesterolemia were ruled out by clinical study, complementary tests and follow-up. The APOB, MTTP and SAR1B genes were sequenced. Patients were found to be heterozygotes for point mutations located in the exon 26 of the APOB gene. One patient, with fatty liver, carried a previously described mutation (c.7600C>T) (Arg2507X), causing the formation of truncated Apo B-55.25. The other two mutations producing truncations are new. One asymptomatic patient carried the Arg3672X (Apo B-80.93) and the other with fatty liver and steatorrhea carried the Ser2184fsVal2193X (Apo B-48.32). Our study reinforces the concept that in the heterozygous carriers of truncated Apo Bs, the clinical manifestations of FHBL are dependent on the size of the truncations.
authors.affiliation: Unidad de Lípidos, Unidad de Gestión Clínica de Medicina Interna, Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Malaga, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Martín-Morales
authors.forename: J D
authors.initials: JD
authors.lastname: García-Díaz
authors.forename: P
authors.initials: P
authors.lastname: Tarugi
authors.forename: P
authors.initials: P
authors.lastname: González-Santos
authors.forename: P
authors.initials: P
authors.lastname: Saavedra-Vallejo
authors.forename: L
authors.initials: L
authors.lastname: Magnolo
authors.forename: J M
authors.initials: JM
authors.lastname: Mesa-Latorre
authors.forename: E
authors.initials: E
authors.lastname: di Leo
authors.forename: P
authors.initials: P
authors.lastname: Valdivielso
mesh_terms: D000328:Adult; D000368:Aged; D001055:Apolipoproteins B / Q000097:blood / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D006995:Hypobetalipoproteinemias / Q000175:diagnosis* / Q000235:genetics*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology; D008297:Male; D009154:Mutation; D013030:Spain; D044465:White People; D055815:Young Adult
chemical_list: D001055:Apolipoproteins B
keywords: ANGPTL3; APOB; Apo B truncations; FHBL; Familial hypobetalipoproteinemia; MTTP; PCSK9; SAR1 homolog B; SAR1B; Steatorrhea; angiopoietin-like 3; apolipoprotein B; familial hypobetalipoproteinemia; microsomal triglyceride transfer protein; proprotein convertase subtilin/kexin type 9