Variants of uncertain significance in the era of next-generation sequencing.
J Am Assoc Nurse Pract
; 34(8): 1018-1021, 2022 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-35731603
ABSTRACT
ABSTRACT Next-generation sequencing (NGS) is now widely used in diagnosing rare diseases. However, it has some limitations, such as variants of uncertain significance (VUS). This can present difficulties even for nurse practitioners involved in clinical genetics. We present three cases from our clinical practice two targeted panel testing and one exome sequencing. Whole blood samples were collected and sent for NGS analysis. In case 1, a VUS was found in the LITAF gene, which is associated with autosomal dominant Charcot-Marie-Tooth disease type 1C. In case 2, a VUS was reported in the MEFV gene, which is associated with autosomal recessive and autosomal dominant familial Mediterranean fever. In these cases, the reported VUS corresponded to the clinical diagnosis. In case 3, two variants in the heterozygous state were found in the ATP7B gene, which is associated with Wilson disease, and the disorder was later clinically recognized. According to the published guidelines, VUSs should not be discussed as a cause for an observed genetic condition. Nevertheless, if the reported variant is in a gene associated with the clinically diagnosed disorder, and there is a strong genotype-phenotype correlation, it could be suggestive of the etiological role of this variant.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doença de Charcot-Marie-Tooth
/
Sequenciamento de Nucleotídeos em Larga Escala
Tipo de estudo:
Diagnostic_studies
/
Guideline
Limite:
Humans
Idioma:
En
Revista:
J Am Assoc Nurse Pract
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Bulgária