Altitude is a phenotypic modifier in hereditary paraganglioma type 1: evidence for an oxygen-sensing defect
Altitude is a phenotypic modifier in hereditary paraganglioma type 1: evidence for an oxygen-sensing defect
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DOI：
10.1007/s00439-003-0969-6
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发表时间：
2003-08-01
期刊：
影响因子：
5.3
通讯作者：
Baysal, BE
中科院分区：
文献类型：
--
作者：
Astrom, K;Cohen, JE;Baysal, BE
遗传性1型副神经节瘤（PGL 1）的特征是生长缓慢和血管化的肿瘤，通常发生在颈动脉体（CB）中，由线粒体复合物II的琥珀酸脱氢酶D（SDHD）基因突变引起。肿瘤发生的机制和影响表达率和表达率的因素尚不清楚。由于在高海拔地区的慢性缺氧刺激引起散发性CB副神经节瘤，它已被假设，SDHD基因产物可能参与氧传感。在此背景下，我们研究了基因型-表型-环境的关系，并测试了较高的海拔是否对PGL 1的表型产生不利影响。对23个家系的58名受试者进行分析，发现无义/剪接突变携带者比错义突变携带者出现症状早8.5年（P
Hereditary paraganglioma type 1 (PGL1) is characterized by slow-growing and vascularized tumors that often develop in the carotid body (CB) and is caused by mutations in the gene for succinate dehydrogenase D (SDHD) of mitochondrial complex II. The mechanisms of tumorigenesis and the factors affecting penetrance and expressivity are unknown. Because chronic hypoxic stimulation at high altitudes causes sporadic CB paragangliomas, it has been hypothesized that the SDHD gene product may be involved in oxygen sensing. On this background, we examined genotype-phenotype-environment relationships and tested whether higher altitudes adversely affect the phenotype in PGL1. An analysis of 58 subjects from 23 families revealed that nonsense/splicing mutation carriers developed symptoms 8.5 years earlier than missense mutation carriers (P