| [PMID]: | 28296734 |
| [Au] Autor: | Guo X; Fan C; Wang Y; Wang M; Cai C; Yang Y; Zhao S; Duan F; Li Y |
| [Ad] Endereço: | aKey Laboratory of Clinical Trial Research in Cardiovascular Drugs, Ministry of Health, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China bAlfred I. DuPont Hospital for Children, Wilmington, DE cDepartment of Radiology dDepartment of Ultrasound, Fuwai Hospital, Beijing, China. |
| [Ti] Título: | Genetic anticipation in a special form of hypertrophic cardiomyopathy with sudden cardiac death in a family with 74 members across 5 generations. |
| [So] Source: | Medicine (Baltimore);96(11):e6249, 2017 Mar. |
| [Is] ISSN: | 1536-5964 |
| [Cp] País de publicação: | United States |
| [La] Idioma: | eng |
| [Ab] Resumo: | Hypertrophic cardiomyopathy (HCM) is the most common heritable heart disease. The genetic anticipation of HCM and its associated etiology, sudden cardiac death (SCD), remains unclear. The aim of this study was to investigate the mechanism underlying the genetic anticipation of HCM and associated SCD.An HCM family including 5 generations and 74 members was studied. Two-dimensional echocardiography was performed to diagnose HCM. The age of onset of HCM was defined as the age at first diagnosis according to hospital records. The information on SCD was confirmed by verification by ≥2 family members and a review of hospital records. Whole-genome sequencing was performed on 4 HCM subjects and 1 healthy control in the family. The identified mutations were screened in all available family members and 216 unrelated healthy controls by Sanger sequencing.The median ages of onset of HCM were 63.5, 38.5, and 18.0 years in members of the second, third, and fourth generations of the family, respectively, and the differences between the generations were significant (P < 0.001). The age at SCD also decreased with each subsequent generation (P < 0.05). In particular, among the third-generation family members, SCD occurred between 30 and 40 years of age at approximately 8 AM, whereas among the fourth-generation family members, all 5 males who experienced SCD were 16 years of age and died at approximately 8 AM. The sarcomere gene mutations MYH7-A719H and MYOZ2-L169G were detected in the HCM individuals in this pedigree. Increases in the number of mutations and the frequency of multiple gene mutations were observed in the younger generations. Moreover, a structural variant was present in the HCM phenotype-positive subjects but was absent in the HCM phenotype-negative subjects.HCM may exhibit genetic anticipation, with a decreased age of onset and increased severity in successive generations. Multiple gene mutations may contribute to genetic anticipation in HCM and thus may be of prognostic value. |
| [Mh] Termos MeSH primário: |
Antecipação Genética
Miosinas Cardíacas/genética
Cardiomiopatia Hipertrófica Familiar/genética
Proteínas de Transporte/genética
Morte Súbita Cardíaca/etiologia
Proteínas Musculares/genética
Cadeias Pesadas de Miosina/genética
|
| [Mh] Termos MeSH secundário: |
Adolescente
Adulto
Idoso
Estudos de Casos e Controles
Criança
Feminino
Estudo de Associação Genômica Ampla
Seres Humanos
Masculino
Meia-Idade
Análise de Sequência de DNA
Adulto Jovem
|
| [Pt] Tipo de publicação: | CASE REPORTS; JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Carrier Proteins); 0 (MYH7 protein, human); 0 (MYOZ2 protein, human); 0 (Muscle Proteins); EC 3.6.1.- (Cardiac Myosins); EC 3.6.4.1 (Myosin Heavy Chains) |
| [Em] Mês de entrada: | 1703 |
| [Cu] Atualização por classe: | 170403 |
[Lr] Data última revisão:
| 170403 |
| [Sb] Subgrupo de revista: | AIM; IM |
| [Da] Data de entrada para processamento: | 170316 |
| [St] Status: | MEDLINE |
| [do] DOI: | 10.1097/MD.0000000000006249 |
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