Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/124211
Title: Age, origin and functional study of the prevalent LDLR mutation causing familial hypercholesterolaemia in Gran Canaria
Authors: Suárez, Nicolás M.
Jebari-Benslaiman, Shifa
Jiménez Monzón,Roberto 
Benito-Vicente, Asier
Brito Casillas, Yeray 
Garcés, Laida
González Lleó, Ana María 
Tugores Céster,Antonio 
Boronat Cortés, Mauro 
Martin, César
Wägner, Anna Maria Claudia 
Sánchez Hernández,Rosa María 
UNESCO Clasification: 32 Ciencias médicas
320102 Genética clínica
320502 Endocrinología
Keywords: Familial hypercholesterolaemia
Founder effect
Gran Canaria
Ldlr gene
Mutation, et al
Issue Date: 2023
Journal: International Journal of Molecular Sciences 
Abstract: The p.(Tyr400_Phe402del) mutation in the LDL receptor (LDLR) gene is the most frequent cause of familial hypercholesterolaemia (FH) in Gran Canaria. The aim of this study was to determine the age and origin of this prevalent founder mutation and to explore its functional consequences. For this purpose, we obtained the haplotypic information of 14 microsatellite loci surrounding the mutation in one homozygous individual and 11 unrelated heterozygous family trios. Eight different mutation carrier haplotypes were identified, which were estimated to originate from a common ancestral haplotype 387 (110–1572) years ago. This estimation suggests that this mutation happened after the Spanish colonisation of the Canary Islands, which took place during the fifteenth century. Comprehensive functional studies of this mutation showed that the expressed LDL receptor was retained in the endoplasmic reticulum, preventing its migration to the cell surface, thus allowing us to classify this LDLR mutation as a class 2a, defective, pathogenic variant.
URI: http://hdl.handle.net/10553/124211
ISSN: 1661-6596
DOI: 10.3390/ijms241411319
Source: International Journal of Molecular Sciences[ISSN 1661-6596],v. 24 (14), (Julio 2023)
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