Autosomal recessive hypercholesterolemia (ARH) is a rare genetic defect that causes marked elevation of plasma low-density lipoprotein cholesterol (LDL-C) and premature atherosclerosis. It is due to mutations in the ARH gene that plays a critical role in the internalization of LDL receptor (LDLR) in liver cells. We describe a Spanish family where a 24-year-old proband and his 13-year-old sister showed the typical characteristics of ARK The proband's LDLR activity in peripheral lymphocytes was 14% of normal and his in vivo LDL catabolism was reduced by 64% compared to normal. Notably, the sister showed normal lipid levels when her umbilical cord blood was tested. In this family, ARH was due to homozygosity for a large similar to 1.6 kb deletion that eliminates exon 4 of ARH gene. Analysis of ARH mRNA demonstrated that the fusion of exon 3 to exon 5 during the splicing of the primary transcript changes the reading frame leading to stop codon 7 amino acids downstream in exon 5. No protein product was detected in affected individuals by immunoblot analysis. This novel mutation adds new support to the molecular heterogeneity of ARH in the Mediterranean basin. (C) 2007 Elsevier Inc. All rights reserved.

Autosomal recessive hypercholesterolemia in Spanish kindred due to a large deletion in the ARH gene / Quagliarini, Fabiana; Joan Carles, Vallve; Campagna, Filomena; Adriana, Alvaro; Francisco Jose Fuentes, Jimenez; Maria Isabella, Sirinian; Francesca, Meloni; Luis, Masana; Arca, Marcello. - In: MOLECULAR GENETICS AND METABOLISM. - ISSN 1096-7192. - STAMPA. - 92:3(2007), pp. 243-248. [10.1016/j.ymgme.2007.06.012]

Autosomal recessive hypercholesterolemia in Spanish kindred due to a large deletion in the ARH gene

QUAGLIARINI, Fabiana;CAMPAGNA, Filomena;ARCA, Marcello
2007

Abstract

Autosomal recessive hypercholesterolemia (ARH) is a rare genetic defect that causes marked elevation of plasma low-density lipoprotein cholesterol (LDL-C) and premature atherosclerosis. It is due to mutations in the ARH gene that plays a critical role in the internalization of LDL receptor (LDLR) in liver cells. We describe a Spanish family where a 24-year-old proband and his 13-year-old sister showed the typical characteristics of ARK The proband's LDLR activity in peripheral lymphocytes was 14% of normal and his in vivo LDL catabolism was reduced by 64% compared to normal. Notably, the sister showed normal lipid levels when her umbilical cord blood was tested. In this family, ARH was due to homozygosity for a large similar to 1.6 kb deletion that eliminates exon 4 of ARH gene. Analysis of ARH mRNA demonstrated that the fusion of exon 3 to exon 5 during the splicing of the primary transcript changes the reading frame leading to stop codon 7 amino acids downstream in exon 5. No protein product was detected in affected individuals by immunoblot analysis. This novel mutation adds new support to the molecular heterogeneity of ARH in the Mediterranean basin. (C) 2007 Elsevier Inc. All rights reserved.
2007
arh protein; autosomal recessive hypercholesterolemia; deletions; genetic hypercholesterolemia
01 Pubblicazione su rivista::01a Articolo in rivista
Autosomal recessive hypercholesterolemia in Spanish kindred due to a large deletion in the ARH gene / Quagliarini, Fabiana; Joan Carles, Vallve; Campagna, Filomena; Adriana, Alvaro; Francisco Jose Fuentes, Jimenez; Maria Isabella, Sirinian; Francesca, Meloni; Luis, Masana; Arca, Marcello. - In: MOLECULAR GENETICS AND METABOLISM. - ISSN 1096-7192. - STAMPA. - 92:3(2007), pp. 243-248. [10.1016/j.ymgme.2007.06.012]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/362388
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