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SURF1-Related Leigh Syndrome (LS) via the SURF1 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
10031 SURF1 81405 81405,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
10031SURF181405 81405,81479 $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 primarily 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, and 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). 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. In the general population, pathogenic variation in the SURF1 gene is one of the most frequent causes of LS associated with cytochrome c oxidase (COX) deficiency (Tiranti et al. 1998; Zhu et al. 1998).

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 (for a review, see 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 SURF1 gene, comprised of nine exons, is thought to encode for an assembly or maintenance factor for the cytochrome c oxidase (COX/complex IV) (Zhu et al. 1998; Tiranti et al. 1999). A number of pathogenic variants (>80) have been documented for SURF1-associated autosomal recessive LS, although the majority of identified mutations cluster within exons 6-8 (for a review, see Wedatilake et al. 2013). Deletions and/or insertions of one or more nucleotides are a common cause of SURF1 gene disruption, usually resulting in frameshifts and premature protein termination. A number of missense mutations, some of which abolish existing splice sites, have also been reported, in addition to several duplication events (Tiranti et al. 1998; Wedatilake et al. 2013). One small deletion (c.845_846delCT) is prevalent among patients with Slavic ancestry (Böhm et al. 2006).

Clinical Sensitivity - Sequencing with CNV PGxome

In the general population, pathogenic variation in the SURF1 gene is one of the most frequent causes of LS associated with cytochrome c oxidase (COX) deficiency (Tiranti et al. 1998; Zhu et al. 1998). 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). Analytical sensitivity of this test is expected to be high, however, as the majority of documented pathogenic variants in SURF1 are detectable by this sequencing test.

Testing Strategy

This test provides full coverage of all coding exons of the SURF1 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

SURF1 sequencing should be considered in patients with a family history of LS or childhood encephalopathy, or patients who present with symptoms consistent with LS. We will also sequence the SURF1 gene to determine carrier status.

Gene

Official Gene Symbol OMIM ID
SURF1 185620
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Leigh Syndrome XL 256000

Related Tests

Name
NDUFA2-Related Leigh Syndrome (LS) via the NDUFA2 Gene
Comprehensive Cardiology Panel
Leigh Syndrome Associated with Isolated Complex I Deficiency via the NDUFA12 Gene
Leigh Syndrome Associated with Mitochondrial Complex I Deficiency via the NDUFA9 Gene
Leigh Syndrome Associated With Mitochondrial Complex I Deficiency via the NDUFAF2 Gene
Leigh Syndrome Associated with Mitochondrial Complex I Deficiency via the NDUFS7 Gene
Mitochondrial Complex I Deficiency Panel (Nuclear Genes)
Mitochondrial Complex I Deficiency via the NDUFS4 Gene
Mitochondrial Complex III Deficiency Panel (Nuclear Genes)
Mitochondrial Complex IV Deficiency via the COX15 Gene

Citations

  • Böhm M et al. 2006. Pediatric Research. 59: 21-6. PubMed ID: 16326995
  • 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
  • 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 IS. and Saneto RP. 2014. The Application of Clinical Genetics. 7: 221-34. PubMed ID: 25419155
  • Tiranti V. et al. 1998. American Journal of Human Genetics. 63: 1609-21. PubMed ID: 9837813
  • Tiranti V. et al. 1999. Human Molecular Genetics. 8: 2533-40. PubMed ID: 10556302
  • Wedatilake Y. et al. 2013. Orphanet Journal of Rare Diseases. 8: 96. PubMed ID: 23829769
  • 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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