A novel splice site variant in the LDLRAP1 gene causes familial hypercholesterolemia

Ahangari, Najmeh, Sahebkar, Amirhossein, Azimi-Nezhad, Mohsen, Ghazizadeh, Hamideh, Moohebati, Mohsen, Ebrahim, Mahmoud, Esmaeili, Habibollah, Ferns, Gordon A, Pasdar, Alireza and Ghayour Mobarhan, Majid (2021) A novel splice site variant in the LDLRAP1 gene causes familial hypercholesterolemia. Iranian Biomedical Journal, 25 (5). pp. 374-379. ISSN 1028-852X

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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.

Item Type: Article
Keywords: Genetic research, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypercholesterolemia, LDLRAP1, Adaptor Proteins, Signal Transducing, Adolescent, Adult, Base Sequence, Chromosome Segregation, Female, Humans, Hyperlipoproteinemia Type II, Male, Middle Aged, Pedigree, Pharmacogenetics, RNA Splice Sites, Young Adult
Schools and Departments: Brighton and Sussex Medical School > Division of Medical Education
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 29 Apr 2022 13:44
Last Modified: 29 Apr 2022 13:45
URI: http://sro.sussex.ac.uk/id/eprint/105572

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