The Ups and Downs of Genetic Diagnosis of Hypertrophic Cardiomyopathy

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• 作者：Juan Gó ; mez^a ; Juliá ; n R. Reguero^b ; Eliecer Coto^a ; ^c ; ^{eliecer.coto@sespa.es" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Hypertrophic cardiomyopathy ; Massive sequencing ; Variant of uncertain significance ; Filamin C
• 刊名：Revista Española de Cardiología (English Edition)
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：69
• 期：1
• 页码：61-68
• 全文大小：443 K

文摘

Massive DNA sequencing, also known as next-generation sequencing, has revolutionized genetic diagnosis. This technology has reduced the effort and cost needed to analyze several genes simultaneously and has made genetic evaluation available to a larger number of patients. In hypertrophic cardiomyopathy, genetic analysis has increased from the 3 main genes implicated in the disease (MYH7, MYBPC3, TNNT2) to sequencing of more than 20 related genes. Despite the advantages of acquiring this additional information, many patients show variants of uncertain significance (mainly amino acid changes), which may also be present in at least 1 healthy control undergoing genome sequencing. This will be a dead-end situation unless the variant can be demonstrated to be associated with the disease in the patient's family. In the absence of clear evidence that these variants are truly pathogenic, they cannot be used for reliable genetic counselling in family members. Massive sequencing also enables identification of new candidate genes, but again, the problem of variants of uncertain significance limits the success of these assessments.