Spastic Paraplegia 72 via the REEP2 Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
2852 REEP2$680.00 81479 Add to Order
Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

Clinical Sensitivity

It is difficult to estimate the clinical sensitivity of this test due to the lack of large cohort studies. The few reported pathogenic variants are detectable by sequencing.

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Clinical Features

Spastic paraplegia 72 (SPG72) is a type of hereditary spastic paraplegia (HSP) that has been described recently in two large families (Esteves et al. 2014). SPG72 has onset of walking difficulty and stiff legs in early childhood. It is relatively "pure", i.e., the symptoms are limited in the lower limbs. Some patients may manifest sphincter disturbances and/or pes cavus. SPG72 is slowly progressive, and some affected individuals may need assistance in walking in their later life (Esteves et al. 2014).   


SPG72 is caused by pathogenic variants in REEP2, and it can be inherited as an autosomal dominant (AD) or autosomal recessive (AR) disorder. Esteves et al identified a missense pathogenic variant (c.107T>A) that segregated in the heterozygous state in a French family with AD inheritance, and two pathogenic variants (c.215T>A and c.105+3G>T) that segregated in trans in a Portuguese family with AR transmission (Esteves et al. 2014). Similar to REEP1REEP2 also encodes a protein of the Reep/DP1/Yop1p family, which is highly expressed in the brain and spinal cord (Hurt et al. 2014). The REEP2 (receptor expression-enhancing protein 2) protein contains two highly conserved hydrophobic N-terminal domains, which can form hairpins that insert into the endoplasmic reticulum (ER) membrane and modulate its curvature (Björk et al. 2013). The two missense variants in REEP2 reported in the Esteves et al study and almost all the missense variants identified so far in REEP1 are located in the N-terminal domains (Esteves et al. 2014; Goizet et al. 2011; Beetz et al. 2008; Human Gene Mutation Database).  

Testing Strategy

This test involves bidirectional Sanger sequencing using genomic DNA of all coding exons of the REEP2 gene plus ~10 bp of flanking non-coding DNA on each side. We will also sequence any single exon (Test #100) or pair of exons (Test #200) in family members of patients with known mutations or to confirm research results. 

Indications for Test

Individuals with symptoms consistent with autosomal dominant HSP, and family members of patients who have known REEP2-HSP mutations are candidates for this test.  


Official Gene Symbol OMIM ID
REEP2 609347
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Spastic Paraplegia 72 AD,AR 615625

Related Tests

Hereditary Spastic Paraplegia Comprehensive Sequencing Panel with CNV Detection
Pure Hereditary Spastic Paraplegia Sequencing Panel with CNV Detection


Genetic Counselors
  • Beetz C et al. 2008. Brain : a Journal of Neurology. 131: 1078-86. PubMed ID: 18321925
  • Björk S. et al. 2013. Plos One. 8: e76366. PubMed ID: 24098485
  • Esteves T. et al. 2014. American Journal of Human Genetics. 94: 268-77. PubMed ID: 24388663
  • Goizet C et al. 2011. Human Mutation. 32: 1118-27. PubMed ID: 21618648
  • Human Gene Mutation Database (Bio-base).
  • Hurt CM. et al. 2014. Brain Research. 1545: 12-22. PubMed ID: 24355597
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Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 10 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of February 2018, we compared 26.8 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 14 years of our lab operation we have Sanger sequenced roughly 14,300 PCR amplicons. Only one error has been identified, and this was an error in analysis of sequence data.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 10 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

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Ordering Options

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.
  • 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.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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