SUCCINATE DEHYDROGENASE COMPLEX SUBUNIT D (SDHD)
Respiratory Chain Complex II Deficiency
Sequencing of the entire coding region of SDHD Gene

Description:

Complex II (succinate-ubiquinone oxidoreductase) is an important enzyme complex in both the tricarboxylic acid cycle and the aerobic respiratory chain of mitochondria in eukaryotic cells. Complex II in human mitochondria has 4 subunits. In order of decreasing molecular weight, they are the flavoprotein (SDHA), the iron-sulfur protein (SDHB), and 2 integral membrane proteins: the large cytochrome b, cybL or C, subunit (SDHC) and the small cybS or D subunit (SDHD). Of the 5 mitochondrial complexes, I to V, complex II is the only one that does not contain any subunits encoded by the mitochondrial genome. Defective mitochondrial respiratory enzymes cause multisystemic disorders with predominantly neuromuscular manifestations. Compared with defects in the other 4 complexes, abnormalities in complex II are rare and the clinical presentation varies among individuals. Enzymatic activity of succinate dehydrogenase (complex II) and succinate: cytochrome c reductase (complex II + complex III) can be measured in tissue samples (muscle or skin fibroblasts, test codes 3200 and 3210). If there is biochemical evidence of complex II deficiency or suspicion for familial cancer DNA analysis of the relevant genes can be performed to confirm the diagnosis. Mutations in the SDHD so far identified are predominantly associated with paragangliomas and pheochromocytomas. The predisposition to cancer is inherited in an autosomal dominant mode, with loss of heterozygosity in tumors. The complex II subunits play a role in the oxygen-sensing pathway and in the regulation of angiogenesis of neural crest-derived tumors. The human SDHD gene maps to chromosome 11q23. It contains 4 exons. To date, more than 40 different mutations have been reported in the HGMD mutation database.

Reasons for Referral:

Confirmation of a clinical diagnosis
Carrier testing

Testing Methodology:

The exons and flanking intronic regions of the SDHD gene are PCR amplified and sequenced in both the forward and reverse directions.

Specimen Requirements:

Blood: EDTA (purple-top) tubes: Adult: 5 cc; Child and Infant: 3 cc

Turnaround Time:

2-4 weeks

CPT Codes and Prices:

Index: 83891, 83894x2, 83904x8, 83898x4, 83912
Known Familial Mutation: 83904x4, 83912, 83898x2, 83891, 83894x2
Panel: 83891, 83894x6, 83904x36, 83898x18, 83912x3

Shipping Information

Forms:

>> Gene Sequencing Requisition, Cancer DNA Requisition, or Mitochondrial Requisition - Mitochondrial Diagnostic Checklist is included

Test Codes:

Index: 3195
Known Familial Mutation: 3196
Panel (SDHB, SDHC, & SDHD): 3600