Hereditary Spastic Paraplegia via the ATP2B4 (PMCA4) 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
4355 ATP2B4 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4355ATP2B481479 81479 $890 Order Options and Pricing

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

Hereditary Spastic Paraplegia (HSP) is a group of clinically and genetically diverse diseases, characterized by spasticity (rigid muscles) and lower extremity weakness (Fink 2014; Hensiek et al. 2015). To date, more than 70 forms of HSP have been described (Tesson et al. 2015). In a two-generation Chinese family with 6 members (4 were symptomatic and 2 were asymptomatic), Li et al. reported a form of autosomal dominant HSP (Li et al. 2014). Affected individuals in this family developed progressive spastic paraplegia since teenage or mid-30s. They manifested weakness in hip and knee flexion, and downgoing plantar responses. The disease seems to be a “pure” type, as the patients’ upper limbs remained unaffected and no cognitive dysfunction was involved (Li et al. 2014).

Genetics

Based on the Chinese family studied, the disease is inherited in an autosomal dominant manner. By whole exome sequencing, Li et al. identified a missense variant (c.803G>A, p.Arg268Gln) in the Plasma Membrane Calcium ATPase gene (PMCA4, also known as ATP2B4) (Li et al. 2014). This is the only pathogenic variant identified so far in the ATP2B4 gene (Human Gene Mutation Database). ATP2B4 is involved in calcium homeostasis (Kunert-Keil et al. 2014), and the p.Arg268Gln pathogenic variant in ATP2B4 may cause delay in intracellular calcium extrusion (Ho 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. The only reported pathogenic variant, c.803G>A, is detectable by sequencing.

Testing Strategy

This test provides full coverage of all coding exons of the ATP2B4 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.

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

Family members of patients with ATP2B4-HSP mutations are candidates of this test. Patients with clinical symptoms consistent with autosomal dominant HSP may consider this test.

Gene

Official Gene Symbol OMIM ID
ATP2B4 108732
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID

Citations

  • Fink J.K. 2014. Seminars in Neurology. 34: 293-305. PubMed ID: 25192507
  • Hensiek A. et al. 2015. Journal of Neurology. 262: 1601-12. PubMed ID: 25480570
  • Ho Philip W.L. 2015. Brain and Behavior. 5: e00321. PubMed ID: 25798335
  • Human Gene Mutation Database (Bio-base).
  • Kunert-Keil C.H. et al. 2014. Journal of Physiology and Pharmacology. 65: 317-24. PubMed ID: 24781740
  • Li M. et al. 2014. Plos One. 9: e104790. PubMed ID: 25119969
  • Tesson C. et al. 2015. Human Genetics. 134: 511-38. PubMed ID: 25758904

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

View Ordering Instructions

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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.

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