Volume 25, Issue 5 (9-2021)                   IBJ 2021, 25(5): 374-379 | Back to browse issues page

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Ahangari N, Sahebkar A, Azimi-Nezhad M, Ghazizadeh H, Moohebati M, Ebrahimi M, et al . A Novel Splice Site Variant in the LDLRAP1 Gene Causes Familial Hypercholesterolemia. IBJ 2021; 25 (5) :374-379
URL: http://ibj.pasteur.ac.ir/article-1-3251-en.html
A Novel Splice Site Variant in the LDLRAP1 Gene Causes Familial Hypercholesterolemia
Najmeh Ahangari , Amirhossein Sahebkar , Mohsen Azimi-Nezhad , Hamideh Ghazizadeh , Mohsen Moohebati , Mahmoud Ebrahimi , Habibillah Esmaeili , Gordon Ferns , Alireza Pasdar , Majid Ghayour Mobarhan
Abstract:  
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.
Keywords: Genetic research, LDLRAP1, Hypercholesterolemia, Hydroxymethylglutaryl-CoA Reductase Inhibitors
Full-Text [PDF 700 kb]      
Type of Study: Case Report | Subject: Molecular Genetics & Genomics
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