AUTHOR=Chang Xiaoyan , Li Zelin , Ma Xiaosen , Cui Yunying , Chen Shuchun , Tong Anli 

TITLE=A Novel Phenotype of Germline Pathogenic Variants in MAX: Concurrence of Pheochromocytoma and Ganglioneuroma in a Chinese Family and Literature Review

JOURNAL=Frontiers in Endocrinology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2020.00558

DOI=10.3389/fendo.2020.00558

ISSN=1664-2392

ABSTRACT=<p><bold>Background:</bold><italic>MYC associated factor X</italic> (<italic>MAX</italic>) is a tumor suppressor gene and has been identified as one of the pathogenic genes of hereditary pheochromocytoma (PCC). To date, there have been no reports of ganglioneuroma (GN) with <italic>MAX</italic> variants.</p><p><bold>Case Presentation:</bold> The proband was a 45-years-old Chinese female with paroxysmal hypertension and palpitations who had undergone adrenalectomy for PCC 14 years ago. Her plasma free normetanephrine and 24-h urinary norepinephrine excretion were significantly increased, and abdominal computed tomography (CT) revealed an irregular mass in the left adrenal region, suggesting a recurrence of PCC. The mass was surgically removed and pathologically diagnosed as PCC with lymph node metastasis. The proband's son suffered from paroxysmal hypertension and palpitations. His plasma free metanephrine levels were normal. CT revealed a mass in the right adrenal. The tumor was surgically removed, and the pathological diagnosis was GN. Genetic testing of peripheral blood DNA revealed that the proband and her son had germline pathogenic <italic>MAX</italic> variant c.C97T, p.Arg33Ter, while proband's parents did not have <italic>MAX</italic> variants. Tumor DNA sequencing showed the same <italic>MAX</italic> variant (c.C97T, p.Arg33Ter) in PCC of the proband and GN of her son, both with retention of heterozygosity. Immunohistochemistry demonstrated loss of MAX protein expression in most tumor cells in PCC of the proband and some Schwannian cells in GN of the proband's son.</p><p><bold>Conclusion:</bold> We report a family with a new clinical phenotype of germline pathogenic variants in <italic>MAX</italic> who developed both PCC and GN. Germline pathogenic variants in <italic>MAX</italic> may contribute to the development of GN. Our findings suggest that it is not just paternally inherited <italic>MAX</italic> variants that can cause tumors.</p>