Genetic Testing for Dilated Cardiomyopathy in Clinical Practice

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• 作者：Neal K. Lakdawala ; MD¹ ; Birgit H. Funke ; PhD² ; ³ ; Samantha Baxter ; MS ; CGC² ; Allison L. Cirino ; MS ; CGC¹ ; Amy E. Roberts ; MD⁴ ; Daniel P. Judge ; MD⁵ ; Nicole Johnson ; MS ; CGC⁵ ; Nancy J. Mendelsohn ; MD⁶ ; Chantal Morel ; MD⁷ ; Melanie Care ; MS ; CGC⁷ ; Wendy K. Chung ; MD⁸ ; Carolyn Jones ; MD ; PhD⁹ ; Apostolos Psychogios ; MD¹⁰ ; Elizabeth Duffy² ; Heidi L. Rehm ; PhD² ; ³ ; Emily White ; MS² ; J.G. Seidman ; PhD¹¹ ; Christine E. Seidman ; MD¹ ; ¹¹ ; ¹² ; Carolyn Y. Ho ; MD¹ ; ^{cho@partners.org}
• 关键词：Clinical genetics ; heart failure ; dilated cardiomyopathy ; sarcomere genes ; lamin A/C
• 刊名：Journal of Cardiac Failure
• 出版年：2012
• 出版时间：April, 2012
• 年：2012
• 卷：18
• 期：4
• 页码：296-303
• 全文大小：223 K

文摘

<h4 class=""h4"">Backgroundh4>Familial involvement is common in dilated cardiomyopathy (DCM) and >40 genes have been implicated in causing disease. However, the role of genetic testing in clinical practice is not well defined. We examined the experience of clinical genetic testing in a diverse DCM population to characterize the prevalence and predictors of gene mutations.<h4 class=""h4"">Methods and Resultsh4>

We studied 264 unrelated adult and pediatric DCM index patients referred to 1 reference lab for clinical genetic testing. Up to 10 genes were analyzed (MYH7, TNNT2, TNNI3, TPM1, MYBPC3, ACTC, LMNA, PLN, TAZ, and LDB3), and 70 % of patients were tested for all genes. The mean age was 26.6 ¡À 21.3 years, and 52 % had a family history of DCM. Rigorous criteria were used to classify DNA variants as clinically relevant (mutations), variants of unknown clinical significance (VUS), or presumed benign. Mutations were found in 17.4 % of patients, commonly involving MYH7, LMNA, or TNNT2 (78 % ). An additional 10.6 % of patients had VUS. Genetic testing was rarely positive in older patients without a family history of DCM. Conversely in pediatric patients, family history did not increase the sensitivity of genetic testing.<h4 class=""h4"">Conclusionsh4>

Using rigorous criteria for classifying DNA variants, mutations were identified in 17 % of a diverse group of DCM index patients referred for clinical genetic testing. The low sensitivity of genetic testing in DCM reflects limitations in both current methodology and knowledge of DCM-associated genes. However, if mutations are identified, genetic testing can help guide family management.