Association of a Novel Homozygous Variant in ABCA1 Gene with Tangier Disease

Tangier disease (TD) is a rare autosomal recessive disorder caused by a variant in the ABCA1 gene, characterized by significantly reduced levels of plasma high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-1 (ApoA-I). TD typically leads to accumulation of cholesterol in the peripheral...

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Detalles Bibliográficos
Autores: Barbosa Gouveia, Bárbara, Fernández Crespo, Silvia, Lazaré Iglesias, Héctor, González Quintela, Arturo, Vázquez Agra, Néstor, Hermida Ameijeiras, Álvaro
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universidad de Santiago de Compostela (USC)
Repositorio:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
Idioma:inglés
OAI Identifier:oai:minerva.usc.gal:10347/38887
Acceso en línea:https://hdl.handle.net/10347/38887
Access Level:acceso abierto
Palabra clave:ABCA1
Tangier disease
High-density lipoprotein
ApoA-I
Bioinformatics
32 Ciencias médicas
Descripción
Sumario:Tangier disease (TD) is a rare autosomal recessive disorder caused by a variant in the ABCA1 gene, characterized by significantly reduced levels of plasma high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-1 (ApoA-I). TD typically leads to accumulation of cholesterol in the peripheral tissues and early coronary disease but with highly variable clinical expression. Herein, we describe a case study of a 59-year-old male patient with features typical of TD, in whom a likely pathogenic variant in the ABCA1 gene was identified by whole-exome sequencing (WES), identified for the first time as homozygous (NM_005502.4: c.4799A>G (p. His1600Arg)). In silico analysis including MutationTaster and DANN score were used to predict the pathogenicity of the variant and a protein model generated by SWISS-MODEL was built to determine how the homozygous variant detected in our patient may change the protein structure and impact on its function. This case study describes a homozygous variant of the ABCA1 gene, which is responsible for a severe form of TD and underlines the importance of using bioinformatics and genomics for linking genotype to phenotype and better understanding and accounting for the functional impact of genetic variations