Title of article :
A Novel Splice Site Variant in the LDLRAP1 Gene Causes Familial Hypercholesterolemia
Author/Authors :
Ahangari ، Najmeh Department of Medical Genetics and Molecular Medicine - Faculty of Medicine - Mashhad University of Medical Sciences , Sahebkar ، Amirhossein Biotechnology Research Center, Pharmaceutical Technology Institute, Neurogenic Inflammation Research Center - Mashhad University of Medical Sciences , Azimi-Nezhad ، Mohsen School of Medicine - Université de Lorraine , Ghazizadeh ، Hamideh Department of Nutrition - Student research committee, International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, School of Medicine, Metabolic Syndrome Research Center - Mashhad University of Medical Sciences , Moohebati ، Mohsen Cardiovascular Research Center, School of Medicine - Mashhad University of Medical Sciences , Ebrahimi ، Mahmoud Cardiovascular Research Center, School of Medicine - Mashhad University of Medical Sciences , Esmaeili ، Habibillah Department of Biostatistics Epidemiology - School of Health, Management Social Determinants of Health Research Center - Mashhad University of Medical Sciences , Ferns ، Gordon a. Division of Medical Education - Brighton and Sussex Medical School , Pasdar ، Alireza Division of Applied Medicine - Medical School - University of Aberdeen , Ghayour Mobarhan ، Majid Department of Nutrition - International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, School of Medicine - Mashhad University of Medical Sciences
Abstract :
Background: FH, a hereditary disorder, is caused by pathogenic variants in the LDLR, APOB, and PCSK9 genes. This study has assessed genetic variants in a family, clinically diagnosed with FH. Methods: A family was recruited from MASHAD study in Iran with possible FH based on the Simon Broom criteria. The DNA sample of an affected individual (proband) was analyzed using WES, followed by bioinformatics and segregation analyses. Results: A novel splice site variant (c.345-2A G) was detected in the LDLRAP1 gene, which was segregated in all affected family members. Moreover, HMGCR rs3846662 g.23092A G was found to be homozygous (G/G) in the proband, probably leading to reduced response to simvastatin and pravastatin. Conclusion: LDLRAP1 c.345-2A G could alter the PTB, which acts as an important part of biological pathways related to lipid metabolism.
Keywords :
Genetic research , LDLRAP1 , Hypercholesterolemia , Hydroxymethylglutaryl , CoA Reductase Inhibitors
Journal title :
Iranian Biomedical Journal(IBJ)
Journal title :
Iranian Biomedical Journal(IBJ)
