RESUMO
INTRODUCTION: In this study, patients suspected of having a clinical diagnosis of Marfan Syndrome (MFS), Loeys-Dietz Syndrome (LDS) and Thoracic Aortic Aneurysms and Dissections (TAAD) were referred for genetic testing and examined for mutations in the FBN1, TGFßR1, TGFßR2 and ACTA2 genes. METHODS: We examined 594 samples from unrelated individuals and different combinations of genes were sequenced, including one or more of the following: FBN1, TGFßR1, TGFßR2, ACTA2, and, in some cases, FBN1 was analyzed by MLPA to detect large deletions. RESULTS: A total of 112 patients had a positive result. Of those, 61 had a clinical diagnosis of MFS, eight had LDS, three had TAAD and 40 patients had clinical features with no specific diagnosis provided. A total of 44 patients had an inconclusive result; of these, 12 patients were referred with a clinical diagnosis of MFS, 4 with LDS and 9 with TAAD and 19 had no clinical diagnosis. A total of 89 mutations were novel. CONCLUSION: This study reveals the rate of detection of variants in several genes associated with MFS, LDS and TAAD. The evaluation of patients by individuals with expertise in the field may decrease the likelihood of ordering unnecessary molecular testing. Nevertheless, genetic testing supports the diagnosis of MFS, LDS and TAAD.
Assuntos
Actinas/genética , Aneurisma Aórtico/diagnóstico , Variação Genética , Síndrome de Marfan/diagnóstico , Proteínas dos Microfilamentos/genética , Receptores de Fatores de Crescimento Transformadores beta/genética , Adolescente , Adulto , Idoso , Aneurisma Aórtico/genética , Aneurisma Aórtico/patologia , Criança , Pré-Escolar , Feminino , Fibrilina-1 , Fibrilinas , Testes Genéticos , Humanos , Lactente , Recém-Nascido , Masculino , Síndrome de Marfan/genética , Pessoa de Meia-Idade , Mutação , Análise de Sequência de DNA , Adulto JovemRESUMO
The future of personalized medicine will hinge on effective management of patient genetic profiles. Molecular diagnostic testing laboratories need to track knowledge surrounding an increasingly large number of genetic variants, incorporate this knowledge into interpretative reports, and keep ordering clinicians up to date as this knowledge evolves. Treating clinicians need to track which variants have been identified in each of their patients along with the significance of these variants. The GeneInsight(SM) Suite assists in these areas. The suite also provides a basis for interconnecting laboratories and clinicians in a manner that increases the scalability of personalized medicine processes.