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Clinical description & molecular modeling of novel MAX pathogenic variant causing pheochromocytoma in family, supports paternal parent-of-origin effect
Cancer Genetics ( IF 1.4 ) Pub Date : 2021-01-19 , DOI: 10.1016/j.cancergen.2021.01.004
John E Richter 1 , S Hines 2 , Pavalan Selvam 3 , Herjot Atwal 3 , Houssam Farres 4 , Thomas R Caulfield 5 , Paldeep S Atwal 3
Affiliation  

The titular member of the MAX network of proteins, MYC-associated factor X (MAX), serves an important regulatory function in transcription of E-box genes associated with cell proliferation, differentiation, and apoptosis. Wild type MAX dimerizes with both MYC and MAD, both of which are members of the MAX network, and can promote or repress cell functions as needed. However, pathogenic variants in MAX are known to upset this balance, leading to uncontrolled oncogenic activity and disease phenotypes such as paragangliomas and pheochromocytomas. We report a 58-year-old male and his 32-year-old daughter, both of which have a history of pheochromocytoma and the unique nonsense MAX variant c.271C>T (p.Q91X). These individuals were diagnosed with pheochromocytomas in their early twenties that were later removed through corrective surgery. The father now presents with recurrent symptoms of hypertension, hyperhidrosis, and headaches, which accompany new pheochromocytomas of his remaining adrenal gland. Pathogenicity of this MAX variant is proven through molecular modeling. The case of this father-daughter pair supports both heritability of pheochromocytoma and the paternal parent-of-origin effect for MAX pathogenic variants.



中文翻译:

引起家族性嗜铬细胞瘤的新型MAX致病变异的临床描述和分子模型,支持父系血统

MAX的蛋白质网络的名义成员,MYC相关因子X(MAX),在与细胞增殖,分化和凋亡相关的E-box基因转录中起着重要的调节作用。野生型MAX与MYC和MAD都二聚化,它们都是MAX网络的成员,并且可以根据需要促进或抑制细胞功能。但是,已知MAX中的致病变异会破坏这种平衡,导致不受控制的致癌活性和疾病表型,如神经节瘤和嗜铬细胞瘤。我们报告一名58岁的男性和他32岁的女儿,这两者有嗜铬细胞瘤的历史和独特的废话MAX变型c.271C> T(p.Q91X)。这些人在二十多岁时被诊断患有嗜铬细胞瘤,后来通过矫正手术将其切除。父亲现在表现出高血压,多汗症和头痛的复发症状,并伴有他剩余的肾上腺的新嗜铬细胞瘤。MAX变体的致病性已通过分子建模证明。这对父女的情况既支持嗜铬细胞瘤的遗传性,又支持MAX致病性变体的父源起源效应。

更新日期:2021-01-22
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