title: A novel type of familial hypercholesterolemia: double heterozygous mutations in LDL receptor and LDL receptor adaptor protein 1 gene.
abstract: BACKGROUND
  Autosomal recessive hypercholesterolemia (ARH) is an extremely rare inherited hypercholesterolemia, the cause of which is mutations in low-density lipoprotein (LDL) receptor adaptor protein 1 (LDLRAP1) gene.
  
  
  METHODS
  A total of 146 heterozygous familial hypercholesterolemic (FH) patients with a mutation in LDLR gene were screened for genes encoding proprotein convertase subtilisin/kexin type 9 (PCSK9) and LDLRAP1.
  
  
  RESULTS
  Among the 146 subjects, we identified a 79-year-old Japanese female with double mutations in LDLR gene (c.2431A>T) and LDLRAP1 gene (c.606dup). Two other relatives with double mutations in those genes in her family were also identified. Although the proband exhibited massive Achilles tendon xanthoma and coronary and aortic valvular disease, serum LDL-C level of subjects with double mutations was similar with that of subjects with single LDLR mutation (284.0±43.5 versus 265.1 ± 57.4 mg/dl).
  
  
  CONCLUSIONS
  Additional mutation in LDLRAP1 may account for severer phenotype in terms of xanthoma and atherosclerotic cardiovascular disease in FH patients.
authors.affiliation: Division of Cardiovascular Medicine, Kanazawa University Graduate School of Medicine, Kanazawa, Japan. ht240z@med.kanazawa-u.ac.jp
authors.forename: Hayato
authors.initials: H
authors.lastname: Tada
authors.forename: Masa-aki
authors.initials: MA
authors.lastname: Kawashiri
authors.forename: Rumiko
authors.initials: R
authors.lastname: Ohtani
authors.forename: Tohru
authors.initials: T
authors.lastname: Noguchi
authors.forename: Chiaki
authors.initials: C
authors.lastname: Nakanishi
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Konno
authors.forename: Kenshi
authors.initials: K
authors.lastname: Hayashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nohara
authors.forename: Akihiro
authors.initials: A
authors.lastname: Inazu
authors.forename: Junji
authors.initials: J
authors.lastname: Kobayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mabuchi
authors.forename: Masakazu
authors.initials: M
authors.lastname: Yamagishi
mesh_terms: D000125:Achilles Tendon / Q000473:pathology; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000235:genetics; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics; D008078:Cholesterol, LDL / Q000097:blood; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000150:complications / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000235:genetics; D011973:Receptors, LDL / Q000235:genetics*; D012697:Serine Endopeptidases / Q000235:genetics; D012720:Severity of Illness Index; D014973:Xanthomatosis / Q000235:genetics / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008078:Cholesterol, LDL; C469745:LDLRAP1 protein, human; D011973:Receptors, LDL; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases