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.
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 FHpatients.
Authors: David N Cooper; Michael Krawczak; Constantin Polychronakos; Chris Tyler-Smith; Hildegard Kehrer-Sawatzki Journal: Hum Genet Date: 2013-07-03 Impact factor: 4.132
Authors: Ariel Brautbar; Emili Leary; Kristen Rasmussen; Don P Wilson; Robert D Steiner; Salim Virani Journal: Curr Atheroscler Rep Date: 2015-04 Impact factor: 5.113
Authors: Akl C Fahed; Ruby Khalaf; Rony Salloum; Rabih R Andary; Raya Safa; Inaam El-Rassy; Elie Moubarak; Sami T Azar; Fadi F Bitar; Georges Nemer Journal: Mol Genet Genomic Med Date: 2016-02-24 Impact factor: 2.183