Gender- and age-related differences in distinct phenotypes of hypertrophic cardiomyopathy-associated mutation MYBPC3–E334K
| Autor: | Qianli Yang, Zhiling Ma, Changhui Lei, Juan Zhang, Xueli Zhao, Liwen Liu, Xuan-Ying Wang, Bo Wang, Lei Zuo, Yue Wang, Xiaoli Zhu, Yanmin Zhang |
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| Rok vydání: | 2021 |
| Předmět: |
Proband
business.industry Hypertrophic cardiomyopathy Physiology Disease 030204 cardiovascular system & hematology medicine.disease Phenotype Penetrance Culprit 03 medical and health sciences 0302 clinical medicine Mutation (genetic algorithm) Genotype Medicine 030212 general & internal medicine Cardiology and Cardiovascular Medicine business |
| Zdroj: | Heart and Vessels. 36:1525-1535 |
| ISSN: | 1615-2573 0910-8327 |
| Popis: | The mutation MYBPC3–E334K is a culprit mutation of hypertrophic cardiomyopathy (HCM). The pathogenicity of MYBPC3–E334K is conflicting in ClinVar because of the limited segregation data and the relatively high frequency in gnomAD (0.03% overall, with 0.3% in East Asians and 0.8% in Japanese). The main aim is to clarify the clinical importance and phenotype–genotype correlations in subjects with or without MYBPC3–E334K alone. The prevalence of MYBPC3–E334K was sequenced in 1017 HCM unrelated probands. The clinical features, morphology phenotypes, and electrical phenotypes were further analyzed according to the phenotype and genotype status in families with single-mutation MYBPC3–E334K. Nine of 1017 (0.88%) unrelated HCM probands were detected harboring MYBPC3–E334K, and three of them harbored a second variant in sarcomere protein gene. Family study and co-segregation analyses indicated that patients with single-mutation MYBPC3–E334K showed autosomal dominant mode of inheritance with incomplete penetrance. The overall disease penetrance was 52.6%, and the disease penetrance was higher in males than in females (100% in men vs 25% in women, p = 0.003). The mean age at diagnosis of males was approximately 25 years younger than females (36.57 ± 18.65 vs 62.33 ± 12.10, p = 0.062). The variant MYBPC3–E334K was classified as a likely pathogenic variant, and a second sarcomere variant did not reveal obvious cumulative effects. The patients harboring single-mutation MYBPC3–E334K had incomplete penetrance, and males demonstrated higher penetrance and early onset HCM than females. A second sarcomere variant did not reveal obvious cumulative effects. |
| Databáze: | OpenAIRE |
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