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Spastic Paraplegia 54 via the DDHD2 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
4895 DDHD2 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4895DDHD281479 81479,81479 $890 Order Options and Pricing

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).

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

  • Greg Fischer, PhD

Clinical Features and Genetics

Clinical Features

Spastic paraplegia 54 (SPG54) is a type of complex hereditary spastic paraplegia (HSP). Patients with SPG54 have spasticity of the lower limbs, delayed psychomotor development, and mild to moderate intellectual disability. The onset is typically before the age of two years. Brain MRI shows a thin corpus callosum and periventricular white matter lesions (Schuurs-Hoeijmakers et al. 2012, 2013; Doi et al. 2014). An accumulation of lipids in basal ganglia and the thalamus is usually detected with cerebral magnetic resonance spectroscopy (MRS). This can be used as a diagnostic biomarker to distinguish this disease with other types of complex HSP (Schuurs-Hoeijmakers et al. 2012).

Genetics

SPG54 is inherited in an autosomal recessive manner, and DDHD2 (DDHD-domain-containing 2) is the causative gene (Schuurs-Hoeijmakers et al. 2012; Gonzales et al. 2013). Similar to DDHD1 (the causative gene for SPG28), DDHD2 also belongs to the mammalian intracellular phospholipase A1 family. The DDHD2 gene encodes a phospholipase that hydrolyzes sn-1 ester bonds of phospholipids, producing 2-acyl-lysophospholipids and fatty acids. The DDHD2 protein may determines membrane curvature and regulate membrane and vesicle fusion through membrane phospholipid hydrolysis (Sato et al. 2010; Inoue et al. 2012). Different types of pathogenic variants (nonsense, missense, splice, and deletions/duplications) have been identified in this gene (Human Gene Mutation Database). Most identified pathogenic variants affect the protein’s DDHD domain, which is important for phospholipase activity.

Clinical Sensitivity - Sequencing with CNV PGxome

It is difficult to estimate the clinical sensitivity of this test due to the lack of large cohort studies. Most of the documented pathogenic variants in DDHD2 gene are detectable by sequencing.

To date, only one gross deletion has been identified in DDHD2 (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the DDHD2 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

Individuals with a complex form of autosomal recessive spastic paraplegia and abnormal lipid accumulation detected by cerebral magnetic resonance spectroscopy (MRS) are candidates for this test. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in DDHD2.

Gene

Official Gene Symbol OMIM ID
DDHD2 615003
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Spastic Paraplegia 54 AR 615033

Citations

  • Doi H. et al. 2014. Scientific Reports. 4: 7132. PubMed ID: 20932832
  • Gonzalez M. et al. 2013. European Journal of Human Genetics. 21: 1214-8. PubMed ID: 23486545
  • Human Gene Mutation Database (Bio-base).
  • Inoue H. et al. 2012. Biochimica Et Biophysica Acta. 1823: 930-9. PubMed ID: 22922100
  • Sato S. et al. 2010. Febs Letters. 584: 4389-95.
  • Schuurs-Hoeijmakers J.H. et al. 2012. American Journal of Human Genetics. 91: 1073-81. PubMed ID: 23176823
  • Schuurs-Hoeijmakers J.H. et al. 2013. Journal of Medical Genetics. 50: 802-11. PubMed ID: 24123876

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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