Genetic spectrum of familial hypercholesterolemia and correlations with clinical expression: Implications for diagnosis improvement.
Clin Genet
; 100(5): 529-541, 2021 11.
Article
en En
| MEDLINE
| ID: mdl-34297352
ABSTRACT
Familial hypercholesterolemia (FH) is the most common genetic disease caused by variants in LDLR, APOB, PCSK9 genes; it is characterized by high levels of LDL-cholesterol and premature cardiovascular disease. We aim to perform a retrospective analysis of a genetically screened population (528 unrelated patients-342 adults and 186 children) to evaluate the biochemical and clinical correlations with the different genetic statuses. Genetic screening was performed by traditional sequencing and some patients were re-analyzed by next-generation-sequencing. Pathogenic variants, mainly missense in the LDLR gene, were identified in 402/528 patients (76.1%), including 4 homozygotes, 17 compound heterozygotes and 1 double heterozygotes. A gradual increase of LDL-cholesterol was observed from patients without pathogenic variants to patients with a defective variant, to patients with a null variant and to patients with two variants. Six variants accounted for 51% of patients; a large variability of LDL-cholesterol was observed among patients carrying the same variant. The frequency of pathogenic variants gradually increased from unlikely FH to definite FH, according to the Dutch Lipid Clinic Network criteria. Genetic diagnosis can help prognostic evaluation of FH patients, discriminating between the different genetic statuses or variant types. Clinical suspicion of FH should be considered even if few symptoms are present or if LDL-cholesterol is only mildly increased.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fenotipo
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Predisposición Genética a la Enfermedad
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Estudios de Asociación Genética
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Hiperlipoproteinemia Tipo II
Tipo de estudio:
Diagnostic_studies
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Prognostic_studies
Límite:
Adult
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Child
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Female
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Humans
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Male
Idioma:
En
Revista:
Clin Genet
Año:
2021
Tipo del documento:
Article
País de afiliación:
Italia