The island of Gran Canaria: A genetic isolate for familial hypercholesterolemia.
J Clin Lipidol
; 13(4): 618-626, 2019.
Article
en En
| MEDLINE
| ID: mdl-31153816
ABSTRACT
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_174936.3c.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.Palabras clave
Texto completo:
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Banco de datos:
MEDLINE
Asunto principal:
Receptores de LDL
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Hiperlipoproteinemia Tipo II
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
País como asunto:
Europa
Idioma:
En
Año:
2019
Tipo del documento:
Article