Spastic Paraplegia 51 via the AP4E1 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
5403 AP4E1 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
5403AP4E181479 81479(x2) $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-51 (SPG51) is a type of hereditary spastic paraplegia (HSP) and is characterized by neonatal muscular hypotonia of all limbs that gradually progresses to spasticity, hypertonia and severe intellectual disability with absent or poor speech development. Some patients may also manifest short stature, seizures and dysmorphic facial features (Moreno-De-Luca et al. 2011; Abou Jamra et al. 2011).

Genetics

SPG51 is inherited in an autosomal recessive (AR) manner and is caused by pathogenic variants in the AP4E1 gene. To date, one nonsense pathogenic variant, one frameshift pathogenic variant and one gross deletion have been identified in SPG51 patients (Moreno-De-Luca et al. 2011; Abou Jamra et al. 2011; Kong et al. 2013). AP4E1 encodes the adaptor-related protein complex 4 epsilon 1 subunit, one of the four subunits of the AP-4 complex. This protein complex plays an important role in brain development and function by regulating the transportation of cargo proteins from the trans-Golgi system to the endosomal–lysosomal network (Hirst et al. 1999). Pathogenic variants in the genes encoding the other three subunits of the AP-4 complex have also been reported in patients with autosomal recessive spastic paraplegia (AP4B1/SPG47, AP4M1/SPG50 and AP4S1/SPG52) (Abou Jamra et al. 2011).

SPG51 is allelic with autosomal dominant stuttering. A whole-exome sequencing study identified two missense variants and one nonsense variant in the AP4E1 gene causing persistent stuttering (Raza et al. 2015).

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. Almost all the pathogenic variants reported to date in AP4E1 gene are detectable by sequencing.

Testing Strategy

This test provides full coverage of all coding exons of the AP4E1 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

Candidates for this test are autosomal recessive spastic paraplegia patients with tetraplegic cerebral palsy, intellectual disability and impaired speech development. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in AP4E1.

Gene

Official Gene Symbol OMIM ID
AP4E1 607244
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Spastic Paraplegia 51 AR 613744

Citations

  • Abou Jamra R. et al. 2011. American Journal of Human Genetics. 88: 788-95. PubMed ID: 21620353
  • Hirst J. et al. 1999. Molecular Biology of the Cell. 10: 2787-802. PubMed ID: 10436028
  • Kong X.F. et al. 2013. Plos One. 8: e58286. PubMed ID: 23472171
  • Moreno-De-Luca A. et al. 2011. Journal of Medical Genetics. 48: 141-4. PubMed ID: 20972249
  • Raza M.H. et al. 2015. American Journal of Human Genetics. 97: 715-25. PubMed ID: 26544806

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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