Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/69919
Title: The island of Gran Canaria: A genetic isolate for familial hypercholesterolemia
Authors: Sánchez Hernández, Rosa María 
Tugores, Antonio 
Nóvoa, Francisco J. 
Brito-Casillas, Yeray 
Expósito-Montesdeoca, Ana B.
Garay, Paloma
Bea, Ana M.
Riaño, Marta
Pocovi, Miguel
Civeira, Fernando
Wägner, Ana M. 
Boronat, Mauro 
Keywords: Canary Islands
Familial Hypercholesterolemia
Founder Effect
Genetic Isolation
Issue Date: 2019
Journal: Journal of Clinical Lipidology 
Abstract: © 2019 National Lipid Association Background: Genetic diagnosis of familial hypercholesterolemia (FH) has not been universally performed in the Canary Islands (Spain). Objectives: This study aimed to genetically characterize a cohort of patients with FH in the island of Gran Canaria. Methods: Study subjects were 70 unrelated index cases attending a tertiary hospital in Gran Canaria, with a clinical diagnosis of FH, according to the criteria of the Dutch Lipid Clinic Network. Given that 7 of the first 10 cases with positive genetic study were carriers of a single mutation in the LDLR gene [p.(Tyr400_Phe402del)], a specific polymerase chain reaction-based assay was developed for the detection of this variant as a first screening step on the remaining subjects. In those without this mutation, molecular diagnosis was completed using a next-generation sequencing panel including LDLR, APOB, PCSK9, LDLRAP1, APOE, STAP1, and LIPA genes and incorporating copy number variation detection in LDLR. Results: On the whole, 44 subjects (62%) had a positive genetic study, of whom 30 (68%) were heterozygous carriers of the p.(Tyr400_Phe402del) variant. Eleven subjects carried other mutations in LDLR, including the novel mutation NM_000527.4: c.877dupG; NP_000518.1: p.(Asp293Glyfs*8). An unclassified PCSK9 gene variant was found in one subject [(NM_174936.3:c.1496G>A; NP_777596.2: p.(Arg499His)]. Other single patients had mutations in APOB (heterozygous) and in LIPA (homozygous). All identified variants co-segregated with the disease phenotype. Conclusions: These findings suggest a founder effect for the p.(Tyr400_Phe402del) LDLR mutation in Gran Canaria. A cost-effective local screening strategy for genetic diagnosis of FH could be implemented in this region.
URI: http://hdl.handle.net/10553/69919
ISSN: 1933-2874
DOI: 10.1016/j.jacl.2019.04.099
Source: Journal of Clinical Lipidology[ISSN 1933-2874],v. 13 (4), p. 618-626
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