| چکیده انگلیسی مقاله |
Background: familial hypercholesterolemia (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 whole exome sequencing, 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 phosphotyrosine-binding domain, which acts as an important part of biological pathways related to lipid metabolism. |
| نویسندگان مقاله |
| Najmeh Ahangari
Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| Amirhossein Sahebkar
Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| Mohsen Azimi-Nezhad
UMR INSERM U 1122, IGE-PCV “Interactions Gène-Environnement en Physiopathologie CardioVasculaire”, Université de Lorraine, 54000, Nancy, France. School of Medicine, Neyshabur University of Medical Sciences, Neyshabur, Iran
| Hamideh Ghazizadeh
Student research committee, Mashhad University of Medical Sciences, Mashhad, Iran; 6International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Department of Nutrition, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| Mohsen Moohebati
Cardiovascular Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| Mahmoud Ebrahimi
Cardiovascular Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| Habibillah Esmaeili
Department of Biostatistics & Epidemiology, School of Health, Management & Social Determinants of Health Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| Gordon Ferns
Division of Medical Education, Brighton and Sussex Medical School, Falmer, Brighton, Sussex, BN1 9PH, UK
| Alireza Pasdar
Division of Applied Medicine, Medical School, University of Aberdeen, Forester hill, Aberdeen, UK
| Majid Ghayour Mobarhan
International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Department of Nutrition, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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