BACKGROUND AND AIM: The complete absence of the lysosomal acid lipase (LAL) enzyme function causes Wolman's Disease that is fatal within the first six months of life. Subtotal defects cause Cholesteryl ester storage disease (CESD), an autosomal recessive disorder leading to hepatic steatosis, fibrosis, micronodular cirrhosis, combined hyperlipidemia with low HDL-cholesterol, increased risk for atherosclerosis, premature death. Since the frequency of the Exon 8 splice junction mutation (c.894 G > A, E8SJM), the CESD leading mutation, is not rare in the general population (allele frequency 0.0025), we investigated the impact of this mutation on serum lipid profile in E8SJM carriers. METHODS AND RESULTS: We collected E8SJM carriers both form genetic study-population analysis and from Outpatient Lipid Clinics and then we assessed their serum lipid profile. We found thirteen individuals heterozygote for E8SJM. Most of them were Germans, three Spanish and two Italian. We found a significant increase in total cholesterol levels in both sexes with E8SJM mutation, leading to a significant increase in LDL cholesterol in males. CONCLUSIONS: Our results show that LAL E8SJM carriers have an alteration in lipid profile with a Polygenic Hypercholesterolemia phenotype, leading to an increase in cardiovascular risk profile.
BACKGROUND AND AIM: The complete absence of the lysosomal acid lipase (LAL) enzyme function causes Wolman's Disease that is fatal within the first six months of life. Subtotal defects cause Cholesteryl ester storage disease (CESD), an autosomal recessive disorder leading to hepatic steatosis, fibrosis, micronodular cirrhosis, combined hyperlipidemia with low HDL-cholesterol, increased risk for atherosclerosis, premature death. Since the frequency of the Exon 8 splice junction mutation (c.894 G > A, E8SJM), the CESD leading mutation, is not rare in the general population (allele frequency 0.0025), we investigated the impact of this mutation on serum lipid profile in E8SJM carriers. METHODS AND RESULTS: We collected E8SJM carriers both form genetic study-population analysis and from OutpatientLipid Clinics and then we assessed their serum lipid profile. We found thirteen individuals heterozygote for E8SJM. Most of them were Germans, three Spanish and two Italian. We found a significant increase in total cholesterol levels in both sexes with E8SJM mutation, leading to a significant increase in LDL cholesterol in males. CONCLUSIONS: Our results show that LAL E8SJM carriers have an alteration in lipid profile with a Polygenic Hypercholesterolemia phenotype, leading to an increase in cardiovascular risk profile.
Authors: Nathan O Stitziel; Sigrid W Fouchier; Barbara Sjouke; Gina M Peloso; Alessa M Moscoso; Paul L Auer; Anuj Goel; Bruna Gigante; Timothy A Barnes; Olle Melander; Marju Orho-Melander; Stefano Duga; Suthesh Sivapalaratnam; Majid Nikpay; Nicola Martinelli; Domenico Girelli; Rebecca D Jackson; Charles Kooperberg; Leslie A Lange; Diego Ardissino; Ruth McPherson; Martin Farrall; Hugh Watkins; Muredach P Reilly; Daniel J Rader; Ulf de Faire; Heribert Schunkert; Jeanette Erdmann; Nilesh J Samani; Lawrence Charnas; David Altshuler; Stacey Gabriel; John J P Kastelein; Joep C Defesche; Aart J Nederveen; Sekar Kathiresan; G Kees Hovingh Journal: Arterioscler Thromb Vasc Biol Date: 2013-09-26 Impact factor: 8.311
Authors: Stuart A Scott; Benny Liu; Irina Nazarenko; Suparna Martis; Julia Kozlitina; Yao Yang; Charina Ramirez; Yumi Kasai; Tommy Hyatt; Inga Peter; Robert J Desnick Journal: Hepatology Date: 2013-07-29 Impact factor: 17.425
Authors: Francesco Baratta; Daniele Pastori; Maria Del Ben; Licia Polimeni; Giancarlo Labbadia; Serena Di Santo; Fiorella Piemonte; Giulia Tozzi; Francesco Violi; Francesco Angelico Journal: EBioMedicine Date: 2015-05-22 Impact factor: 8.143
Authors: Francesco Baratta; Daniele Pastori; Licia Polimeni; Giulia Tozzi; Francesco Violi; Francesco Angelico; Maria Del Ben Journal: Int J Mol Sci Date: 2015-11-25 Impact factor: 5.923