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| Germline pathogenic MAX variants in this family. (A) Genetic testing indicated that the proband and her son had a germline pathogenic MAX variant (c.C97T, p.Arg33Ter). (B) Pedigree of a family with PCC and GN. Other familial members including parents of the proband, her husband, and two daughters did not have MAX variants.
Source publication
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 w...
Contexts in source publication
Context 1
... genomic DNA of the proband was examined for potential pathogenic germline variants of PCC by next-generation sequencing covering SDHA, SDHB, SDHC, SDHD, SDHAF2, VHL, RET, MAX, TMEM127, FH, NF1, and KIF1B. A germline MAX variant (c.C97T, p.Arg33Ter) was identified and confirmed by Sanger sequencing ( Figure 3A). The proband's son had the same germline variant, which was detected by Sanger sequencing of the coding sequences of exon 3 of MAX. ...
Context 2
... proband's son had the same germline variant, which was detected by Sanger sequencing of the coding sequences of exon 3 of MAX. Other familial members including parents of the proband, her husband, and two daughters did not have MAX variants ( Figure 3B). The minor allele frequency (MAF) of the MAX variant (c.C97T, p.Arg33Ter) is not specified. ...
Citations
... Among 499 studies, 213 articles reported variants related to PPGLs and 16 papers reported MAX variants. We summarized the characteristics of the cases with PPGLs in MAX variants [5,15,16,[19][20][21][22][23][24][25][26][27][28][29][30][31] (Supplementary Table S1). Combining data from the 16 reports in MAX variants revealed that 42/71 cases (59.2%) had bilateral PCCs, 9/59 cases (8.5%) had PGLs, and 31/70 cases (44.3%) had an apparent family history of PPGLs. ...
Recently, the genetic background of pheochromocytomas/paragangliomas (PPGLs) has been rapidly revealed. These tumors have been referred to as the “ten percent tumor”; however, the frequency of genetic variants of PPGLs has turned out to be more common than expected. PPGLs are potentially hereditary tumors and appear clinically sporadic. Here, we report a case of bilateral pheochromocytoma (PCC) with a variant in the MYC-associated factor X (MAX) gene (c.295 + 1G > A). A male patient was diagnosed with adrenal pheochromocytoma (PCC) and underwent a left adrenalectomy at the age of 40. A new tumor in the right adrenal gland was detected at the age of 43. Urinary metanephrine and normetanephrine concentrations gradually increased. The size of the right adrenal PCC continued to increase one year after detection. Genetic testing of the peripheral blood revealed the presence of a pathogenic variant in MAX. The natural history of adrenal PCCs with the MAX variant has not yet been clarified, because the number of reported cases is not sufficient. Thus, clinicians should consider a MAX variant when they find bilateral or multiple PCCs.
... MAX has been recently described at a total of~40 PPGLs (9,(32)(33)(34). In our study, 6 patients had MAX variant, with the ratio being 1.9% in all PPGL patients. ...
Pheochromocytoma/paraganglioma (PPGL) has a high genetic heterogeneity with 40% germline variants in known pathogenic genes. Data in Chinese on this aspect are scanty. To detect the genetic and clinical profile of Chinese PPGL patients, we examined the variants of 12 known germline pathogenic genes (SDHA, SDHB, SDHC, SDHD, SDHAF2, FH, VHL, RET, NF1, MAX, TMEM127, and KIF1B) by next-generation sequencing and Sanger sequencing in 314 Chinese PPGL subjects. Twenty nine percent of Chinese PPGL patients had germline variants and SDHB was the most frequently mutated (14.6%). The most frequent SDHB variants were in exon 2, exon 7, and IVS 7. Pathogenic variants were more likely to occur in metastatic PPGL patients, paragangliomas, and patients under 30, with the ratio being 50.7% (35/69), 35.9% (56/156), and 49.5% (52/105), respectively. Our cohort included 314 patients from a single setting. The genetic and clinical features of Chinese PPGL patients were unique in some aspects compared to their non-Chinese counterparts. Identification of genotype-phenotype relation can serve as an effective tool for genetic prioritization and clinical decision-making.
