Clinical description & molecular modeling of novel MAX pathogenic variant causing pheochromocytoma in family, supports paternal parent-of-origin effect

John E. Richter, S. Hines, Pavalan Selvam, Herjot Atwal, Houssam Farres, Thomas R. Caulfield, Paldeep S. Atwal

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)107-110
Number of pages4
JournalCancer Genetics
Volume252-253
DOIs
StatePublished - Apr 2021

Keywords

  • C.271C>T (p.q91x)
  • MYC-associated factor X (MAX)
  • Protein modeling

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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