Xinquan Lian, Liping Shen, Jiayin Song, Mengqi Pang, Yunmeng Zhong, Han Zhang, Yadong Xing, Tao-Hsin Tung, Bo Shen
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引用次数: 0
Abstract
Background: Germline pathogenic variants (PVs) of succinate dehydrogenase subunit D (SDHD) are major genetic causes of pheochromocytomas and paragangliomas. Existing studies have reported inconsistent findings and lack a comprehensive synthesis regarding penetrance, multifocality and metastatic risk in carriers of SDHD PVs.
Objective: To systematically assess age-specific penetrance (in all carriers) and the proportions of multifocality, metastatic disease and mortality among affected carriers, and explore potential genotype-phenotype associations through a systematic review and meta-analysis.
Methods: Eligible observational studies were selected from PubMed, MEDLINE and EMBASE that reported age-specific penetrance (in all carriers) and the proportions of multifocality, metastatic disease and mortality among affected carriers (those with tumours). Additionally, data on specific SDHD variants associated with tumour multifocality or metastatic behaviour were collected. Following independent data extraction and quality assessment by two reviewers, these proportions were meta-analysed using random-effects models or fixed-effect model to generate pooled estimates with 95% CIs and prediction intervals.
Results: Age-specific penetrance increased from 20% at 20 years of age (95% CI 16% to 25%) to 58% at 40 years (95% CI 48% to 67%) and 82% at 60 years (95% CI 75% to 90%). Among the affected SDHD PV carriers, the pooled proportions were 75% (95% CI 72% to 79%) for multifocal tumours, 3% (95% CI 2% to 4%) for metastatic disease and 1% (95% CI 1% to 2%) for mortality.
Conclusion: SDHD PV carriers exhibit increasing age-specific penetrance, with a high proportion of patients having multifocal tumours but low proportions of metastatic disease and mortality, providing partial evidence for the need for lifelong monitoring of SDHD PV carriers. However, evidence linking specific variants to these phenotypes is limited and requires further investigation.
期刊介绍：
Journal of Medical Genetics is a leading international peer-reviewed journal covering original research in human genetics, including reviews of and opinion on the latest developments. Articles cover the molecular basis of human disease including germline cancer genetics, clinical manifestations of genetic disorders, applications of molecular genetics to medical practice and the systematic evaluation of such applications worldwide.
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