Spastic Paraplegia 51 via the AP4E1 Gene
Summary and Pricing
Test Method
Exome Sequencing with CNV DetectionTest Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
---|---|---|---|---|---|
5403 | AP4E1 | 81479 | 81479,81479 | $990 | 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 platform).
Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).
Turnaround Time
3 weeks on average for standard orders or 2 weeks 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.
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.
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
If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.
Specimen Types
Specimen Requirements and Shipping Details
PGxome (Exome) Sequencing Panel
PGnome (Genome) Sequencing Panel
ORDER OPTIONS
View Ordering Instructions1) Select Test Type
2) Select Additional Test Options
No Additional Test Options are available for this test.