A novel type of familial hypercholesterolemia: Double heterozygous mutations in LDL receptor and LDL receptor adaptor protein 1 gene

作者：Tada Hayato^*; Kawashiri Masa aki; Ohtani Rumiko; Noguchi Tohru; Nakanishi Chiaki; Konno Tetsuo; Hayashi Kenshi; Nohara Atsushi; Inazu Akihiro; Kobayashi Junji; Mabuchi Hiroshi; Yamagishi Masakazu

来源：Atherosclerosis, 2011, 219(2): 663-666.

DOI：10.1016/j.atherosclerosis.2011.08.004

• Autosomal recessive hypercholesterolemia
• Low density lipoprotein receptor adopter protein 1
• Familial hypercholesterolemia
• PCSK9

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).
Conclusion: Additional mutation in LDLRAP1 may account for severer phenotype in terms of xanthoma and atherosclerotic cardiovascular disease in FH patients.

• 出版日期2011-12