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TACO1-Related Leigh Syndrome (LS) via the TACO1 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
8699 TACO1 81404 81404,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8699TACO181404 81404,81479 $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information.

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

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

18 days on average for standard orders or 13 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

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

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Kym Bliven, PhD

Clinical Features and Genetics

Clinical Features

Leigh Syndrome (LS), also known as subacute necrotizing encephalomyelopathy, is a severe neurodegenerative disorder resulting from defects in the mitochondrial respiratory chain (Ruhoy and Saneto 2014; Zhu et al. 1998; Leigh 1951). The disease incidence for LS is estimated to be around 1:32,000 to 1:40,000 live births (Darin et al. 2001; Rahman et al. 1996).

The hallmark features that characterize this syndrome include elevated levels of lactate in blood and cerebral spinal fluid, in addition to the presence of bilateral symmetric necrotic lesions in the basal ganglia, brain stem, thalamus, and/or spinal cord (Wedatilake et al. 2013; Leigh 1951). Patients also present with isolated or combined mitochondrial complex deficiencies, psychomotor delay or regression, and neurologic manifestations such as hypotonia or ataxia. The term ‘Leigh-Like Syndrome (LLS)’ is used to describe a similar clinical presentation in which one or more of these diagnostic characteristics is atypical.

Symptomatic onset of this disorder usually occurs shortly after birth or within the first three years of life, although cases of adult-onset LS/LLS have been reported (Ronchi et al. 2011). LS/LLS infants often present with feeding difficulties, gastrointestinal distress, hypotonia, and growth delays, while older children (>1 years) may develop additional symptoms including developmental regression (loss of cognitive or motor skills), dysphagia, hypertrichosis, dystonic posturing, nystagmus, and opthalmoplegia (Wedatilake et al. 2013).

LS and LLS have been linked to pathogenic variants in over 60 different genes (Rahman 2015). While defects in certain genes are more likely to result in classic LS rather than atypical LLS, genotype-phenotype correlations are still poorly understood. TACO1-associated LLS due to isolated Complex IV (COX) deficiency has been reported in multiple patients from two unrelated families (Weraarpachai et al. 2009; Seeger et al. 2010; Makrythanasis et al. 2014). In one family, affected individuals had a relatively late-onset (4-16 years) LLS with wide variability in symptom severity (Seeger et al. 2010).

Genetics

Leigh and Leigh-Like Syndromes (LS/LLS) are caused by defects in the mitochondrial oxidative phosphorylation (OXPHOS) complexes or associated proteins, such as the OXPHOS assembly factors or components of the pyruvate dehydrogenase (PDH) complex (Rahman 2015). As a result, the LS/LLS phenotypes exhibit significant genetic heterogeneity, and pathogenic variants in over 60 different genes have been reported to be causative for this disorder. Depending on the cellular localization of the affected gene(s), these syndromes may be inherited in an autosomal recessive, maternal, or X-linked recessive manner.

Nuclear genes associated with autosomal recessive inheritance of LS/LLS include: SURF1, BCS1L, C12ORF65, COX10, COX15, FOXRED1, GFM1, LRPPRC, NDUFA2, NDUFA4, NDUFA9, NDUFA10, NDUFA11, NDUFA12, NDUFAF2, NDUFAF5, NDUFAF6, NDUFS1, NDUFS2, NDUFS3, NDUFS4, NDUFS7, NDUFS8, NDUFV1, PDSS2, PET100, SCO2, SDHA, SDHAF1, SLC19A3, SUCLA2, SUCLG1, TACO1, TTC19, UQCRQ, SERAC1, NDUFV2, MTFMT, HIBCH, TSFM, ECHS1, LIAS, PNPT1, POLG, LIPT1, DLD, TPK1, and ETHE1.

Mitochondrial genes associated with maternal inheritance of LS/LLS include: MT-ATP6, MT-TL1, MT-TK, MT-TW, MT-TV, MT-ND1, MT-ND2, MT-ND3, MT-ND4, MT-ND5, MT-ND6, and MT-CO3 .

X-linked genes associated with X-linked recessive inheritance of LS/LLS include: NDUFA1, AIFM1, PDHA1, PDHB, and PDHX. In this form of inheritance, male patients are more frequently affected, although heterozygous females may present with LS/LLS due to skewed X-inactivation (Patel et al. 2012).

The five-exon TACO1 gene encodes for a mitochondrial translational activator that is essential for the synthesis of the mitochondrial DNA (mtDNA)-encoded COX I subunit (Weraarpachai et al. 2009). Two pathogenic variants, both resulting in premature protein truncation, have been reported in TACO1 (Weraarpachai et al. 2009; Makrythanasis et al. 2014).

Clinical Sensitivity - Sequencing with CNV PGxome

At this time, due to the limited number of reported cases, the clinical sensitivity of TACO1-related Leigh Syndrome is difficult to estimate.

Testing Strategy

This test provides full coverage of all coding exons of the TACO1 gene 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. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

TACO1 sequencing should be considered in patients with symptoms consistent with LS/LLS or a family history of childhood encephalopathy, particularly if the individual is negative for plausible causative variants in SURF1 or other commonly reported LS/LLS genes. We will also sequence the TACO1 gene to determine carrier status.

Gene

Official Gene Symbol OMIM ID
TACO1 612958
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Mitochondrial Complex IV Deficiency AR,MT 220110

Related Tests

Name
Mitochondrial Complex IV Deficiency via the COA3 Gene
Mitochondrial Complex IV Deficiency via the COA8/APOPT1 Gene
Mitochondrial Complex IV Deficiency via the COX14 Gene
Mitochondrial Complex IV Deficiency via the COX20 Gene
Mitochondrial Complex IV Deficiency via the COX6B1 Gene
Mitochondrial Complex IV Deficiency via the FASTKD2 Gene
Mitochondrial Complex IV Deficiency via the SCO1 Gene

Citations

  • Darin N. et al. 2001. Annals of Neurology. 49: 377-83. PubMed ID: 11261513
  • Leigh D. 1951. Journal of Neurology, Neurosurgery, and Psychiatry. 14: 216-21. PubMed ID: 14874135
  • Makrythanasis P. et al. Human Mutation. 35:1203-10. PubMed ID: 25044680
  • Patel K. et al. 2012. Molecular Genetics and Metabolism. 105: 34-43. PubMed ID: 22079328
  • Rahman S. 2015. Nuclear Gene-Encoded Leigh Syndrome Overview. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 26425749
  • Rahman S. et al. 1996. Annals of Neurology. 39:343-51. PubMed ID: 8602753
  • Ronchi D. et al. 2011. Biochemical and Biophysical Research Communications. 412: 245-8. PubMed ID: 21819970
  • Ruhoy I. and Saneto R. 2014. The Application of Clinical Genetics. 7: 221-34. PubMed ID: 25419155
  • Seeger J. et al. 2010. Neuromuscular Disorders. 20:720-4. PubMed ID: 20727754
  • Wedatilake Y. et al. 2013. Orphanet Journal of Rare Diseases. 8: 96. PubMed ID: 23829769
  • Weraarpachai W. et al. 2009. Nature Genetics. 41:833-7. PubMed ID: 19503089
  • Zhu Z. et al. 1998. Nature Genetics. 20: 337-43. PubMed ID: 9843204

Ordering/Specimens

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.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

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

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: $
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