Mitochondrial Complex II Deficiency Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
3457 SDHA 81479,81479 Order Options and Pricing
SDHAF1 81479,81479
SDHB 81405,81479
SDHD 81404,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
3457Genes x (4)81479 81404, 81405, 81479 $1090 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


Clinical Features and Genetics

Clinical Features

Isolated mitochondrial complex II (CII) deficiency, a deficit of one of the five oxidative phosphorylation complexes of the mitochondrial respiratory chain, has been associated with a diverse spectrum of clinical disease (Hoekstra and Bayley 2013). In all patients, enzymatic activity of the mitochondrial CII (also referred to as succinate dehydrogenase) is severely reduced in muscle biopsies and cultured fibroblasts.

Leigh syndrome, isolated cardiomyopathy, and infantile leukoencephalopathy are early-onset phenotypes commonly associated with isolated mitochondrial CII deficiency. Patients generally present in infancy or childhood. Leigh syndrome, also known as subacute necrotizing encephalopathy, is characterized by elevated levels of lactate in blood and cerebral spinal fluid; bilateral symmetric necrotic lesions in the basal ganglia, brain stem, thalamus, and/or spinal cord; psychomotor delay or regression; and neurologic manifestations such as hypotonia or ataxia (Wedatilake et al. 2013; Leigh 1951). Alternatively, a small subset of patients present with isolated cardiomyopathy accompanied by mild increases in lactate (Hoekstra and Bayley 2013; Levitas et al. 2010). Finally, defects in mitochondrial CII genes may result in an infantile leukoencephalopathy phenotype, with mild to severe lactic acidosis (Helman et al. 2016; Ghezzi et al. 2009).

Loss of mitochondrial CII activity may also contribute to tumor development, and CII deficiency has been linked to hereditary paraganglioma-pheochromocytoma, gastrointestinal stromal tumor (GIST) development, and renal cell carcinoma (Hoekstra and Bayley 2013; Rutter et al. 2010). For more information regarding hereditary paraganglioma-pheochromocytoma syndrome, see the Hereditary Paraganglioma-Pheochromocytoma Syndrome Sequencing Panel test.


Mitochondrial complex II deficiency is the result of defects in the assembly or function of the succinate dehydrogenase (complex II) of the mitochondrial respiratory chain (Hoekstra and Bayley 2013). Complex II (CII) consists of four structural subunits (SDHA, SDHB, SDHC, and SDHD), while at least two accessory factors (SDHAF1 and SDHAF2) play roles in complex II assembly. Two additional accessory factors (SDHAF3 and SDHAF4) may also contribute to complex maturation, although their respective roles in this process have been less well defined (Na et al. 2014; Van Vranken et al. 2014).

This panel covers four nuclear-encoded genes that have been linked to mitochondrial CII deficiency to date (SDHA, SDHB, SDHD, and SDHAF1). SDHC and SDHAF2, which have only been associated with hereditary paraganglioma, are not included in this panel but are available either as single gene tests or via the Hereditary Paraganglioma-Pheochromocytoma Syndrome Sequencing Panel.

While disorders such as Leigh syndrome, cardiomyopathy, and infantile leukoencephalopathy are inherited in an autosomal recessive manner, familial paraganglioma may be inherited in an autosomal dominant manner with variable expressivity and age-related penetrance (Hoekstra and Bayley 2013).

SDHA: The 15-exon SDHA gene encodes for the flavoprotein subunit of the mitochondrial CII. Over 40 pathogenic variants have been reported in the SDHA gene to date (Human Gene Mutation Database). The majority of these variants are missense changes, although nonsense and splicing variants have been described, as well as a number of small deletions or insertions and one large deletion.

SDHB: The eight-exon SDHB gene encodes for the iron-sulfur cluster subunit of the mitochondrial CII. Over 200 pathogenic variants have been described in this gene to date, the majority of which are missense variants or deletions (HGMD).

SDHD: The four-exon SDHD gene encodes for an integral membrane structural subunit of the mitochondrial CII. Over 150 pathogenic variants, primarily missense changes, nonsense variants, and deletions, have been reported in this gene (HGMD).

SDHAF1: The single-exon SDHAF1 gene encodes for an LYR-family assembly factor that mediates maturation of SDHB, the iron-sulfur cluster subunit of mitochondrial CII (Na et al. 2014; Maio et al. 2016). Four pathogenic variants have been reported in the SDHAF1 gene, including three missense changes and one nonsense change (Ghezzi et al. 2009; Ohlenbusch et al. 2012).

Clinical Sensitivity - Sequencing with CNV PGxome

Isolated complex II deficiency is considered a rare form of mitochondrial disease, accounting for approximately 2-23% of all respiratory chain deficiencies (Parfait et al. 2000; Vladutiu and Heffner 2000). Clinical sensitivity for this test is difficult to estimate, however, as no large cohort studies have been reported.

Clinical testing for large deletions and duplications is difficult to predict as no large cohort studies are available.

Only one gross deletion has been described in SDHA to date (Helman et al. 2016).

In a cohort of 24 paraganglioma patients, large deletions in SDHB were reported in 3 individuals (~12%) who previously tested negative for point mutations in paraganglioma-related genes (Cascón et al. 2006).

At the present time, gross deletion/insertion frequencies for the SDHD gene are unknown, although approximately 15 large deletions and one complex rearrangement have been reported in the SDHD gene to date (Human Gene Mutation Database).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel provides 100% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing.

Due to homology issues, the entire coding region of SDHA (exons 1-15), in addition to ~10 bp of adjacent noncoding sequence of each exon, is bi-directionally sequenced using Sanger sequencing technology. Exon 4 of SDHD is also covered using Sanger sequencing technology.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Candidates for this test include patients with a deficiency of mitochondrial complex II, or those who present with symptoms consistent with a known disease phenotype.


Official Gene Symbol OMIM ID
SDHA 600857
SDHAF1 612848
SDHB 185470
SDHD 602690
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Mitochondrial Complex II Deficiency AR 252011

Related Test



  • Cascón A. et al. 2006. Genes, Chromosomes & Cancer. 45: 213-9. PubMed ID: 16258955
  • Ghezzi D. et al. 2009. Nature Genetics. 41:654-6. PubMed ID: 19465911
  • Helman G. et al. 2016. Annals of Neurology. 79:379-86. PubMed ID: 26642834
  • Hoekstra A.S. and Bayley J.P. 2013. Biochimica et Biophysica Acta. 1827:543-51. PubMed ID: 23174333
  • Human Gene Mutation Database (Bio-base).
  • Leigh D. 1951. Journal of Neurology, Neurosurgery, and Psychiatry. 14:216-21. PubMed ID: 14874135
  • Levitas A. et al. 2010. European Journal of Human Genetics. 18:1160-5. PubMed ID: 20551992
  • Maio N. et al. 2016. Cellular Metabolism. 23:292-302. PubMed ID: 26749241
  • Na U. et al. 2014. Cellular Metabolism. 20:253-66. PubMed ID: 24954417
  • Ohlenbusch A. et al. 2012. Orphanet Journal of Rare Diseases. 7:69. PubMed ID: 22995659
  • Parfait B. et al. 2000. Human Genetics. 106:236-43. PubMed ID: 10746566
  • Rutter J. et al. 2010. Mitochondrion. 10:393-401. PubMed ID: 20226277
  • Van Vranken J.G. et al. 2014. Cellular Metabolism. 20:241-52. PubMed ID: 24954416
  • Vladutiu G.D. and Heffner R.R. 2000. Archives of Pathology & Laboratory Medicine. 124:1755-8. PubMed ID: 11100052
  • Wedatilake et al. 2013. PubMed ID: 23829769


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

Specimen Types

Specimen Requirements and Shipping Details

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STAT and Prenatal Test Options are not available with Patient Plus.

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