Heat Shock 27 kDa Protein-Related Disorders via the HSPB1 Gene
Summary and Pricing 
Test Method
Exome Sequencing with CNV Detection
| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 9177 | HSPB1 | 81404 | 81404,81479 | $990 | Order Options and Pricing |
Pricing Comments
Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.
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).
The Sanger Sequencing method for this test is NY State approved.
For Sanger Sequencing click here.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
Charcot-Marie-Tooth disease type 2F (CMT2F; OMIM 606595) and distal hereditary motor neuronopathy type IIB (HMN2B; OMIM 608634) represent a phenotypic continuum of distal neuropathy with weakness and wasting starting in the distal limbs. In CMT2F distal sensory loss is evident while in HMN2B it is not, thus differentiating the two disorders (Houlden et al. Neurology 71:1660-1668, 2008). Among affected members of the first reported CMT2F family, clinical signs first appeared between 15 and 25 years of age (Ismailov et al. Eur J Hum Genet 9:646-650, 2001). Depressed or absent deep tendon reflexes were present early. Muscle weakness and atrophy of the lower leg resulted in foot drop and steppage gait. Later, atrophy of the upper limb muscles causing claw-hand deformity was evident, and mild to moderate sensory impairments occurred in the feet and hands in all the patients.
Genetics
A family demonstrating autosomal dominant inheritance of axonal type Charcot-Marie-Tooth disease (Ismailov et al. 2001), was later found to have a missense variant in the gene that encodes the heat shock 27 kDa protein (HSPB1, OMIM 602195; Evgrafov et al Nat Genet 36:602-606, 2004). Subsequently, patients with distal hereditary motor neuronopathy were found to have HSPB1 variants (Evgrafov et al. 2004). HSPB1-related CMT and distal HMN are inherited as autosomal dominant disorders, although reports of recessive inheritance and de novo dominant variants are known (Houlden et al. 2008).
Clinical Sensitivity - Sequencing with CNV PGxome
Among a cohort of 301 individuals with CMT and 115 with dHMN, Evgrafov et al. (2004) found HSPB1 variants in 4 families with dHMN and one with CMT. Tang et al. (Arch Neurol 62:1201-1207, 2005) identified an HSPB1 founder variant (p.Cys379Thr) among a cohort of 114 unrelated Chinese CMT patients.
Testing Strategy
This test provides full coverage of all coding exons of the HSPB1 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 clinical symptoms consistent with a distal neuropathy with or without distal sensory loss.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| HSPB1 | 602195 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Diseases
| Name | Inheritance | OMIM ID |
|---|---|---|
| Charcot-Marie-Tooth Disease Type 2F | 606595 | |
| Distal Hereditary Motor Neuronopathy Type 2B | 608634 |
Citations
- Evgrafov, O. V., et.al. (2004). "Mutant small heat-shock protein 27 causes axonal Charcot-Marie-Tooth disease and distal hereditary motor neuropathy." Nat Genet 36(6): 602-6. PubMed ID: 15122254
- Evgrafov, O. V., et.al. (2004). "Mutant small heat-shock protein 27 causes axonal Charcot-Marie-Tooth disease and distal hereditary motor neuropathy." Nat Genet 36(6): 602-6. PubMed ID: 15122254
- Houlden, H., et.al. (2008). "Mutations in the HSP27 (HSPB1) gene cause dominant, recessive, and sporadic distal HMN/CMT type 2." Neurology 71(21): 1660-8. PubMed ID: 18832141
- Houlden, H., et.al. (2008). "Mutations in the HSP27 (HSPB1) gene cause dominant, recessive, and sporadic distal HMN/CMT type 2." Neurology 71(21): 1660-8. PubMed ID: 18832141
- Ismailov, S. M., et.al. (2001). "A new locus for autosomal dominant Charcot-Marie-Tooth disease type 2 (CMT2F) maps to chromosome 7q11-q21." Eur J Hum Genet 9(8): 646-50. PubMed ID: 11528513
- Ismailov, S. M., et.al. (2001). "A new locus for autosomal dominant Charcot-Marie-Tooth disease type 2 (CMT2F) maps to chromosome 7q11-q21." Eur J Hum Genet 9(8): 646-50. PubMed ID: 11528513
- Tang, B., et.al. (2005). "Mutation analysis of the small heat shock protein 27 gene in chinese patients with Charcot-Marie-Tooth disease." Arch Neurol 62(8): 1201-7. PubMed ID: 16087758
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
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ORDER OPTIONS
View Ordering Instructions1) Select Test Type
2) Select Additional Test Options
No Additional Test Options are available for this test.