9] Human genes: TH, tyrosine hydroxylase; DBH, dopamine beta-hydroxylase; PNMT, phenylethanolamine N-methyltransferase; SDH3, succinate dehydrogenase complex iron sulfur subunit B; SDHD
, succinate dehydrogenase complex subunit D; VHL, von Hippel-Lindau tumor suppressor; RET, ret proto-oncogene.
The MAX, PRKAR1A, SDHA, SDHAF2, SDHB, SDHC, SDHD
, TMEM127, and VHL genes were analysed by PCR and next-generation sequencing of both DNA strands of the entire coding region and the highly conserved exon-intron splice junctions was performed.
Sequencing of SDHB, SDHC, or SDHD
is required if a tumor shows a loss of SDHB staining and intact SDHA staining.
38) SDHC and SDHD
mutations are typically associated with head and neck paragangliomas.
In contrast, tumors due to von Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase (VHL) and succinate dehydrogenase complex, subunit B, iron sulfur (Ip) (SDHB) or succinate dehydrogenase complex, subunit D, integral membrane protein (SDHD
) mutations lack increases in metanephrine and in patients with VHL mutations are characterized bysolitary increases in normetanephrine; additional increases in methoxytyramine characterize 70% of tumors due to mutations of SDHD
All other genetic tests were not clearly identified as high priority (MET, FH, FLCN, TSC1, TSC2, SDHD
, SDHC, SDHB, SDHA, PTEN).
Life is much improved on SDHD
at one's own home during the most convenient time according to the day's schedule.
Immunohistochemistry with SDHA and SDHB is useful (and, perhaps, even required) for the diagnosis of SDH-deficient RCC; loss of cytoplasmic SDHA staining indicates a mutation in SDHA, whereas loss of cytoplasmic SDHB staining signifies a mutation in either SDHB, SHDC, or SDHD
Additional genes encoding the SDHD
(succinate dehydrogenase complex, subunit D, integral membrane protein) gene and the newly described TMEM127 (transmembrane protein 127) and MAX (MYC associated factor X) tumor suppressor genes are also known to contribute to the pathogenesis of PCC (5).
11] Human genes: VHL, von Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase; SDHD
, succinate dehydrogenase complex, subunit D, integral membrane protein; MAX, MYC associated factor X; TMEM 127, transmembrane protein 127; SDHA, succinate dehydrogenase complex, subunit A, flavoprotein (Fp).
performed six times a week for only 2 hours has a higher weekly removal of urea than longer treatments of 4 hours, three times a week.
37) Mutations in other genes encoding SDH subunits, particularly SDHD
, have also been associated with head and neck paragangliomas, but paragangliomas associated with SDHD
mutations are almost always benign.