1. Founder mutation identified in the LDLR gene causing familial hypercholesterolemia associated with increased risk of coronary heart disease
Basic science research. Presentation Type: Oral presentation. Introduction: Coronary artery diseases (CAD) inflict heavy economical and social cost on most populations including Saudi’s and contribute significantly to their morbidity and mortality rates. Familial hypercholesterolemia (FH) is heredit...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Saudi Heart Association
2017-10-01
|
| Series: | Journal of the Saudi Heart Association |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1016731517300775 |
| _version_ | 1819319799228923904 |
|---|---|
| author | Faisal Al-Allaf Mohammad Athar Abdullah Alashwal Zainularifeen Abduljaleel Taher Mohiuddin Abdellatif Bouazzaoui Halah Abalkhail Rakan Own Ahmad Al-Allaf Iman Abumansour Zohor Azhar Fahad Alnouri Mawaddah Toonsi |
| author_facet | Faisal Al-Allaf Mohammad Athar Abdullah Alashwal Zainularifeen Abduljaleel Taher Mohiuddin Abdellatif Bouazzaoui Halah Abalkhail Rakan Own Ahmad Al-Allaf Iman Abumansour Zohor Azhar Fahad Alnouri Mawaddah Toonsi |
| author_sort | Faisal Al-Allaf |
| collection | DOAJ |
| description | Basic science research.
Presentation Type: Oral presentation.
Introduction: Coronary artery diseases (CAD) inflict heavy economical and social cost on most populations including Saudi’s and contribute significantly to their morbidity and mortality rates. Familial hypercholesterolemia (FH) is hereditary in an autosomal dominant disease and is a major risk factor for the development of CAD. FH is predominantly caused by variants in the low-density lipoprotein (LDL) receptor gene (LDLR).
Methodology: More than 140 FH samples including 44 probands were collected from 17 unrelated Saudi families who live in the central, northern, western and eastern regions of Saudi Arabia. Patient samples were screened using Next-generation sequencing (NGS) and Capillary sequencing. We described the genetic analysis of severely affected homozygous FH patients who were mostly resistant to statin therapy and were managed on an apheresis program.
Results: We identified a common frameshift mutation p. (G676Afs*33) in exon 14 of the LDLR gene in 17 probands and their first-degree blood relatives in apparently unrelated Saudi families. This founder mutation was found in about 40% Saudi FH population. We also describe a three dimensional homology model of the LDL receptor protein (LDLR) structure and examine the consequence of the frameshift mutation p. (G676Afs*33), as this could affect the LDLR structure in a region involved in dimer formation, and protein stability.
Conclusion: This finding of a recurrent mutation causing FH in the Saudi population could serve to develop a rapid genetic screening procedure for FH, and the 3D-structure analysis of the mutant LDLR, may provide tools to develop a mechanistic model of the LDLR function. |
| first_indexed | 2024-12-24T11:09:25Z |
| format | Article |
| id | doaj.art-f40b7cfc3fb5438e887e7b4e6a470b54 |
| institution | Directory Open Access Journal |
| issn | 1016-7315 |
| language | English |
| last_indexed | 2024-12-24T11:09:25Z |
| publishDate | 2017-10-01 |
| publisher | Saudi Heart Association |
| record_format | Article |
| series | Journal of the Saudi Heart Association |
| spelling | doaj.art-f40b7cfc3fb5438e887e7b4e6a470b542022-12-21T16:58:34ZengSaudi Heart AssociationJournal of the Saudi Heart Association1016-73152017-10-0129431810.1016/j.jsha.2017.06.0131. Founder mutation identified in the LDLR gene causing familial hypercholesterolemia associated with increased risk of coronary heart diseaseFaisal Al-AllafMohammad AtharAbdullah AlashwalZainularifeen AbduljaleelTaher MohiuddinAbdellatif BouazzaouiHalah AbalkhailRakan OwnAhmad Al-AllafIman AbumansourZohor AzharFahad AlnouriMawaddah ToonsiBasic science research. Presentation Type: Oral presentation. Introduction: Coronary artery diseases (CAD) inflict heavy economical and social cost on most populations including Saudi’s and contribute significantly to their morbidity and mortality rates. Familial hypercholesterolemia (FH) is hereditary in an autosomal dominant disease and is a major risk factor for the development of CAD. FH is predominantly caused by variants in the low-density lipoprotein (LDL) receptor gene (LDLR). Methodology: More than 140 FH samples including 44 probands were collected from 17 unrelated Saudi families who live in the central, northern, western and eastern regions of Saudi Arabia. Patient samples were screened using Next-generation sequencing (NGS) and Capillary sequencing. We described the genetic analysis of severely affected homozygous FH patients who were mostly resistant to statin therapy and were managed on an apheresis program. Results: We identified a common frameshift mutation p. (G676Afs*33) in exon 14 of the LDLR gene in 17 probands and their first-degree blood relatives in apparently unrelated Saudi families. This founder mutation was found in about 40% Saudi FH population. We also describe a three dimensional homology model of the LDL receptor protein (LDLR) structure and examine the consequence of the frameshift mutation p. (G676Afs*33), as this could affect the LDLR structure in a region involved in dimer formation, and protein stability. Conclusion: This finding of a recurrent mutation causing FH in the Saudi population could serve to develop a rapid genetic screening procedure for FH, and the 3D-structure analysis of the mutant LDLR, may provide tools to develop a mechanistic model of the LDLR function.http://www.sciencedirect.com/science/article/pii/S1016731517300775 |
| spellingShingle | Faisal Al-Allaf Mohammad Athar Abdullah Alashwal Zainularifeen Abduljaleel Taher Mohiuddin Abdellatif Bouazzaoui Halah Abalkhail Rakan Own Ahmad Al-Allaf Iman Abumansour Zohor Azhar Fahad Alnouri Mawaddah Toonsi 1. Founder mutation identified in the LDLR gene causing familial hypercholesterolemia associated with increased risk of coronary heart disease Journal of the Saudi Heart Association |
| title | 1. Founder mutation identified in the LDLR gene causing familial hypercholesterolemia associated with increased risk of coronary heart disease |
| title_full | 1. Founder mutation identified in the LDLR gene causing familial hypercholesterolemia associated with increased risk of coronary heart disease |
| title_fullStr | 1. Founder mutation identified in the LDLR gene causing familial hypercholesterolemia associated with increased risk of coronary heart disease |
| title_full_unstemmed | 1. Founder mutation identified in the LDLR gene causing familial hypercholesterolemia associated with increased risk of coronary heart disease |
| title_short | 1. Founder mutation identified in the LDLR gene causing familial hypercholesterolemia associated with increased risk of coronary heart disease |
| title_sort | 1 founder mutation identified in the ldlr gene causing familial hypercholesterolemia associated with increased risk of coronary heart disease |
| url | http://www.sciencedirect.com/science/article/pii/S1016731517300775 |
| work_keys_str_mv | AT faisalalallaf 1foundermutationidentifiedintheldlrgenecausingfamilialhypercholesterolemiaassociatedwithincreasedriskofcoronaryheartdisease AT mohammadathar 1foundermutationidentifiedintheldlrgenecausingfamilialhypercholesterolemiaassociatedwithincreasedriskofcoronaryheartdisease AT abdullahalashwal 1foundermutationidentifiedintheldlrgenecausingfamilialhypercholesterolemiaassociatedwithincreasedriskofcoronaryheartdisease AT zainularifeenabduljaleel 1foundermutationidentifiedintheldlrgenecausingfamilialhypercholesterolemiaassociatedwithincreasedriskofcoronaryheartdisease AT tahermohiuddin 1foundermutationidentifiedintheldlrgenecausingfamilialhypercholesterolemiaassociatedwithincreasedriskofcoronaryheartdisease AT abdellatifbouazzaoui 1foundermutationidentifiedintheldlrgenecausingfamilialhypercholesterolemiaassociatedwithincreasedriskofcoronaryheartdisease AT halahabalkhail 1foundermutationidentifiedintheldlrgenecausingfamilialhypercholesterolemiaassociatedwithincreasedriskofcoronaryheartdisease AT rakanown 1foundermutationidentifiedintheldlrgenecausingfamilialhypercholesterolemiaassociatedwithincreasedriskofcoronaryheartdisease AT ahmadalallaf 1foundermutationidentifiedintheldlrgenecausingfamilialhypercholesterolemiaassociatedwithincreasedriskofcoronaryheartdisease AT imanabumansour 1foundermutationidentifiedintheldlrgenecausingfamilialhypercholesterolemiaassociatedwithincreasedriskofcoronaryheartdisease AT zohorazhar 1foundermutationidentifiedintheldlrgenecausingfamilialhypercholesterolemiaassociatedwithincreasedriskofcoronaryheartdisease AT fahadalnouri 1foundermutationidentifiedintheldlrgenecausingfamilialhypercholesterolemiaassociatedwithincreasedriskofcoronaryheartdisease AT mawaddahtoonsi 1foundermutationidentifiedintheldlrgenecausingfamilialhypercholesterolemiaassociatedwithincreasedriskofcoronaryheartdisease |