Iranian Biomedical Journal
مجله بیومدیکال ایران
IBJ
Basic Sciences
http://ibj.pasteur.ac.ir
1
admin
1028-852X
2008-823X
-
10.61186/ibj
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8888
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en
jalali
1400
6
1
gregorian
2021
9
1
25
5
online
1
fulltext
en
A Novel Splice Site Variant in the LDLRAP1 Gene Causes Familial Hypercholesterolemia
Molecular Genetics & Genomics
Molecular Genetics & Genomics
مقاله موردی
Case Report
<strong>Background:</strong> familial hypercholesterolemia (FH), a hereditary disorder, is caused by pathogenic variants in the <em>LDLR</em>, <em>APOB</em>, and <em>PCSK9</em> genes. This study has assessed genetic variants in a family, clinically diagnosed with FH. <strong>Methods:</strong> 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. <strong>Results:</strong> A novel splice site variant (c.345-2A>G) was detected in the <em>LDLRAP1 </em>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. <strong>Conclusion:</strong> <em>LDLRAP1</em> c.345-2A>G could alter the phosphotyrosine-binding domain, which acts as an important part of biological pathways related to lipid metabolism.
Genetic research, LDLRAP1, Hypercholesterolemia, Hydroxymethylglutaryl-CoA Reductase Inhibitors
374
379
http://ibj.pasteur.ac.ir/browse.php?a_code=A-10-3953-2&slc_lang=en&sid=1
Najmeh
Ahangari
najmeh.ahangari@gmail.com
100319475328460054114
100319475328460054114
No
Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Amirhossein
Sahebkar
amir_saheb2000@yahoo.com
100319475328460054115
100319475328460054115
No
Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
Mohsen
Azimi-Nezhad
aziminm@mums.ac.ir
100319475328460054116
100319475328460054116
No
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
ghazizadehh981@mums.ac.ir
100319475328460054117
100319475328460054117
No
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
MouhebatiM@mums.ac.ir
100319475328460054118
100319475328460054118
No
Cardiovascular Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Mahmoud
Ebrahimi
EbrahimiMH@mums.ac.ir
100319475328460054119
100319475328460054119
No
Cardiovascular Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Habibillah
Esmaeili
EsmailyH@mums.ac.ir
100319475328460054120
100319475328460054120
No
Department of Biostatistics & Epidemiology, School of Health, Management & Social Determinants of Health Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Gordon
Ferns
G.Ferns@bsms.ac.uk
100319475328460054121
100319475328460054121
No
Division of Medical Education, Brighton and Sussex Medical School, Falmer, Brighton, Sussex, BN1 9PH, UK
Alireza
Pasdar
pasdara@mums.ac.ir
100319475328460054122
100319475328460054122
No
Division of Applied Medicine, Medical School, University of Aberdeen, Forester hill, Aberdeen, UK
Majid
Ghayour Mobarhan
ghyourm@mums.ac.ir
100319475328460054123
100319475328460054123
Yes
International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Department of Nutrition, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran