Article-v25n5p374-en.pdf (701.44 kB)
A novel splice site variant in the LDLRAP1 gene causes familial hypercholesterolemia
journal contribution
posted on 2023-06-10, 03:17 authored by Najmeh Ahangari, Amirhossein Sahebkar, Mohsen Azimi-Nezhad, Hamideh Ghazizadeh, Mohsen Moohebati, Mahmoud Ebrahim, Habibollah Esmaeili, Gordon FernsGordon Ferns, Alireza Pasdar, Majid Ghayour MobarhanBackground: 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.
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Publication status
- Published
File Version
- Published version
Journal
Iranian Biomedical JournalISSN
1028-852XPublisher
Pasteur Institute of IranExternal DOI
Issue
5Volume
25Page range
374-379Event location
IranDepartment affiliated with
- Division of Medical Education Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2022-04-29First Open Access (FOA) Date
2022-04-29First Compliant Deposit (FCD) Date
2022-04-29Usage metrics
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