Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0031511 (
pheochromocytoma
)
14,622
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Hereditary
pheochromocytoma
(
PCC
) is often caused by germline mutations in one of nine susceptibility genes described to date, but there are familial cases without mutations in these known genes. We sequenced the exomes of three unrelated individuals with hereditary
PCC
(cases) and identified mutations in MAX, the MYC associated factor X gene. Absence of
MAX protein
in the tumors and loss of heterozygosity caused by uniparental disomy supported the involvement of MAX alterations in the disease. A follow-up study of a selected series of 59 cases with
PCC
identified five additional MAX mutations and suggested an association with malignant outcome and preferential paternal transmission of MAX mutations. The involvement of the MYC-MAX-MXD1 network in the development and progression of neural crest cell tumors is further supported by the lack of functional MAX in rat
PCC
(PC12) cells and by the amplification of MYCN in neuroblastoma and suggests that loss of MAX function is correlated with metastatic potential.
...
PMID:Exome sequencing identifies MAX mutations as a cause of hereditary pheochromocytoma. 2168 15
Background:
MYC associated factor X
(
MAX
) 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
MAX
variants.
Case Presentation:
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
MAX
variant c.C97T, p.Arg33Ter, while proband's parents did not have
MAX
variants. Tumor DNA sequencing showed the same
MAX
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.
Conclusion:
We report a family with a new clinical phenotype of germline pathogenic variants in
MAX
who developed both
PCC
and GN. Germline pathogenic variants in
MAX
may contribute to the development of GN. Our findings suggest that it is not just paternally inherited
MAX
variants that can cause tumors.
...
PMID:A Novel Phenotype of Germline Pathogenic Variants in
MAX
: Concurrence of Pheochromocytoma and Ganglioneuroma in a Chinese Family and Literature Review. 3297 81
