Leigh and Leigh-Like Syndrome Panel (Nuclear Genes Only)

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
3453 AIFM1 81479,81479 Order Options and Pricing
BCS1L 81405,81479
COQ9 81479,81479
COX10 81405,81479
COX15 81405,81479
COX8A 81479,81479
DLAT 81406,81479
DLD 81406,81479
EARS2 81479,81479
ECHS1 81479,81479
ETHE1 81479,81479
FARS2 81479,81479
FBXL4 81479,81479
FOXRED1 81479,81479
GFM1 81479,81479
GFM2 81479,81479
GTPBP3 81479,81479
HIBCH 81479,81479
IARS2 81479,81479
LIAS 81479,81479
LIPT1 81479,81479
LRPPRC 81479,81479
MTFMT 81479,81479
MTRFR 81479,81479
NARS2 81479,81479
NDUFA1 81404,81479
NDUFA10 81479,81479
NDUFA12 81479,81479
NDUFA2 81479,81479
NDUFA4 81479,81479
NDUFA9 81479,81479
NDUFAF2 81404,81479
NDUFAF4 81479,81479
NDUFAF5 81479,81479
NDUFAF6 81479,81479
NDUFS1 81406,81479
NDUFS2 81479,81479
NDUFS3 81479,81479
NDUFS4 81404,81479
NDUFS7 81405,81479
NDUFS8 81405,81479
NDUFV1 81405,81479
NDUFV2 81479,81479
NUBPL 81479,81479
PDHA1 81406,81405
PDHB 81405,81479
PDHX 81406,81479
PDSS2 81479,81479
PET100 81479,81479
PNPT1 81479,81479
POLG 81406,81479
SCO2 81404,81479
SDHAF1 81479,81479
SERAC1 81479,81479
SLC19A3 81479,81479
SUCLA2 81479,81479
SUCLG1 81479,81479
SURF1 81405,81479
TACO1 81404,81479
TPK1 81479,81479
TSFM 81479,81479
TTC19 81479,81479
UQCRQ 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
3453Genes x (63)81479 81404, 81405, 81406, 81479 $990 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.

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Leigh Syndrome (LS), also known as subacute necrotizing encephalomyelopathy, is a severe neurodegenerative disorder resulting primarily from defects in the mitochondrial respiratory chain (Ruhoy and Saneto. 2014. PubMed ID: 25419155; Zhu et al. 1998. PubMed ID: 9843204; Leigh. 1951. PubMed ID: 14874135). The disease incidence for LS is estimated to be around 1:32,000 to 1:40,000 live births (Darin et al. 2001. PubMed ID: 11261513; Rahman et al. 1996. PubMed ID: 8602753).

The hallmark features that characterize this syndrome are elevated levels of lactate in blood and cerebral spinal fluid, and the presence of bilateral symmetric necrotic lesions in the basal ganglia, brain stem, thalamus, and/or spinal cord (Wedatilake et al. 2013. PubMed ID: 23829769; Leigh. 1951. PubMed ID: 14874135). 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.

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. PubMed ID: 21819970). 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. PubMed ID: 23829769). LS and LLS have been linked to pathogenic variants in over 60 different genes (Rahman and Thorburn. 2015. PubMed ID: 26425749). However, while defects in certain genes are more likely to result in classic LS rather than atypical LLS, genotype-phenotype correlations are still poorly understood.

Genetics

Leigh and Leigh-Like Syndromes (LS/LLS) are caused by defects in the mitochondrial oxidative phosphorylation (OXPHOS) complexes or associated proteins, such as OXPHOS assembly factors or the pyruvate dehydrogenase (PDH) complex (Rahman and Thorburn. 2015. PubMed ID: 26425749). 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. Please note that genes located in the mitochondrial genome are currently not included in this panel.

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. PubMed ID: 22079328).

Clinical Sensitivity - Sequencing with CNV PGxome

In the general population, pathogenic variation in the SURF1 gene is one of the most frequent causes of Leigh Syndrome (LS) associated with cytochrome c oxidase (COX) deficiency (Tiranti et al. 1998. PubMed ID: 9837813; Zhu et al. 1998. PubMed ID: 9843204). One large cohort study was complicated by the presence of a founder mutation in the affected population, resulting in a high prevalence of SURF1-related LS that is likely not representative of the general population (Böhm et al. 2006. PubMed ID: 16326995).

Overall sensitivity of this panel is difficult to predict, as no large cohort studies have been published to date. For more information regarding predicted clinical sensitivity for a number of the genes involved in this panel, please refer to Rahman and Thorburn (2015. PubMed ID: 26425749).

Testing Strategy

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

This panel typically provides 99.5% 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 coverage as ≥20X NGS reads or Sanger sequencing.

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

This test could be considered in patients with a family history of LS or childhood encephalopathy, or patients who present with symptoms consistent with LS.

Diseases

Name Inheritance OMIM ID
3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-like Syndrome AR 614739
Basal Ganglia Disease, Biotin-Responsive AR 607483
Beta-Hydroxyisobutyryl-CoA Deacylase Deficiency AR 250620
Cardioencephalomyopathy, Fatal Infantile, due to Cytochrome c Oxidase Deficiency 1 AR 604377
Cataracts, Growth Hormone Deficiency, Sensory Neuropathy, Sensorineural Hearing Loss, and Skeletal Dysplasia AR 616007
Coenzyme Q10 deficiency, primary, 3 AR 614652
Coenzyme Q10 Deficiency, Primary, 5 AR 614654
Combined Oxidative Phosphorylation Deficiency 1 AR 609060
Combined Oxidative Phosphorylation Deficiency 12 AR 614924
Combined Oxidative Phosphorylation Deficiency 13 AR 614932
Combined oxidative phosphorylation deficiency 14 AR 614946
Combined Oxidative Phosphorylation Deficiency 15 AR 614947
Combined Oxidative Phosphorylation Deficiency 23 AR 616198
Combined Oxidative Phosphorylation Deficiency 24 AR 616239
Combined Oxidative Phosphorylation Deficiency 3 AR 610505
Combined Oxidative Phosphorylation Deficiency 6 XL 300816
Combined Oxidative Phosphorylation Deficiency 7 AR 613559
Dihydrolipoamide dehydrogenase deficiency AR 246900
Ethylmalonic Encephalopathy AR 602473
Leigh Syndrome XL 256000
Leigh Syndrome, French Canadian Type AR 220111
Lipoyltransferase 1 Deficiency AR 616299
Mitochondrial Complex I Deficiency XL 252010
Mitochondrial Complex III Deficiency, Nuclear Type 2 AR 615157
Mitochondrial Complex III Deficiency, Nuclear Type 4 AR 615159
Mitochondrial Complex IV Deficiency AR, MT 220110
Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type) AR 615471
Mitochondrial DNA Depletion Syndrome 4B, Mngie Type AR 613662
Mitochondrial DNA Depletion Syndrome 5 (Encephalomyopathic with or without Methylmalonic Aciduria) AR 612073
Mitochondrial DNA Depletion Syndrome 9 (Encephalomyopathic With Methylmalonic Aciduria) AR 245400
Mitochondrial Short-Chain Enoyl-CoA Hydratase 1 Deficiency AR 616277
Progressive External Ophthalmoplegia With Mitochondrial DNA Deletions 1 AD 157640
Progressive External Ophthalmoplegia With Mitochondrial DNA Deletions, Autosomal Recessive AR 258450
Progressive Sclerosing Poliodystrophy AR 203700
Pyruvate Dehydrogenase E1-Alpha Deficiency XL 312170
Pyruvate Dehydrogenase E1-Beta Deficiency AR 614111
Pyruvate Dehydrogenase E2 Deficiency AR 245348
Pyruvate Dehydrogenase E3-Binding Protein Deficiency AR 245349
Pyruvate Dehydrogenase Lipoic Acid Synthetase Deficiency AR 614462
Sensory Ataxic Neuropathy, Dysarthria, And Ophthalmoparesis AR 607459
Thiamine Metabolism Dysfunction Syndrome 5 (Episodic Encephalopathy Type) AR 614458

Related Test

Name
PGxome®

Citations

  • Böhm et al. 2006. PubMed ID: 16326995
  • Darin et al. 2001. PubMed ID: 11261513
  • Leigh. 1951. PubMed ID: 14874135
  • Patel et al. 2012. PubMed ID: 22079328
  • Rahman and Thorburn. 2015. PubMed ID: 26425749
  • Rahman et al. 1996. PubMed ID: 8602753
  • Ronchi et al. 2011. PubMed ID: 21819970
  • Ruhoy and Saneto. 2014. PubMed ID: 25419155
  • Tiranti et al. 1998. PubMed ID: 9837813
  • Wedatilake et al. 2013. PubMed ID: 23829769
  • Zhu et al. 1998. 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.

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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ORDER OPTIONS

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2) Select Additional Test Options

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

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