Titre
Identification of a de novo LRP1 mutation in a Saudi family with Tetralogy of Fallot.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Alrayes, N.
Auteure/Auteur
Mallah, B.A.
Auteure/Auteur
Issa, N.M.
Auteure/Auteur
Banaganapalli, B.
Auteure/Auteur
Ahmad Shaik, N.
Auteure/Auteur
Nasser, K.K.
Auteure/Auteur
Alshehri, B.A.
Auteure/Auteur
Bhuiyan, Z.A.
Auteure/Auteur
Bdier, A.Y.
Auteure/Auteur
Al-Aama, J.Y.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1879-0038
Statut éditorial
Publié
Date de publication
2023-01-30
Volume
851
Première page
146909
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
Tetralogy of Fallot (TOF) is a rare, complex congenital heart defect caused by genetic and environmental interactions that results in abnormal heart development during the early stages of pregnancy. Genetic basis of TOF in Saudi populations is not yet studied. Therefore, the objective of this study is to screen for the molecular defects causing TOF in Saudi patients.
A family with non-syndromic TOF was recruited from the Western region of Saudi Arabia. Whole exome sequencing (WES) was performed on the proband and her parents. The identified candidate variant was verified by sanger sequencing. Also, different computational biology tools were used to figure out how candidate variants affect the structure and function of candidate protein involved in TOF.
A novel heterozygous de novo mutation in LRP1 (p. G3311D) gene was identified in the index case. Also, this variant was absent in the in-house exome sequencing data of 80 healthy Saudi individuals. This variant was predicted to be likely pathogenic, as it negatively affects the biophysical chemical properties and stability of the protein. Furthermore, functional biology data from knock out mouse models confirms that molecular defects in LRP1 gene leads to cardiac defects and lethality. This variant was not previously reported in both Arab and global population genetic databases.
The findings in this study postulate that the LRP1 variant has a role in TOF pathogenesis and facilitate accurate diagnosis as well as the understanding of underlying molecular mechanisms and pathophysiology of the disease.
A family with non-syndromic TOF was recruited from the Western region of Saudi Arabia. Whole exome sequencing (WES) was performed on the proband and her parents. The identified candidate variant was verified by sanger sequencing. Also, different computational biology tools were used to figure out how candidate variants affect the structure and function of candidate protein involved in TOF.
A novel heterozygous de novo mutation in LRP1 (p. G3311D) gene was identified in the index case. Also, this variant was absent in the in-house exome sequencing data of 80 healthy Saudi individuals. This variant was predicted to be likely pathogenic, as it negatively affects the biophysical chemical properties and stability of the protein. Furthermore, functional biology data from knock out mouse models confirms that molecular defects in LRP1 gene leads to cardiac defects and lethality. This variant was not previously reported in both Arab and global population genetic databases.
The findings in this study postulate that the LRP1 variant has a role in TOF pathogenesis and facilitate accurate diagnosis as well as the understanding of underlying molecular mechanisms and pathophysiology of the disease.
PID Serval
serval:BIB_F1287CBEA2FB
PMID
Date de création
2022-10-03T12:34:07.043Z
Date de création dans IRIS
2025-05-21T05:14:34Z