MYH3-Related Distal Arthrogryposis via the MYH3 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 | |
---|---|---|---|---|---|
11485 | MYH3 | 81479 | 81479,81479 | $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
Distal arthrogryposis (DA) syndromes are a group of multiple congenital contracture disorders with distal joint involvement, variable clinical expression, and autosomal dominant inheritance (Bamshad et al. Am J Med Genet 65:277- 281, 1996). Distal arthrogryposis 2A (DA2A, OMIM 193700), or Freeman-Sheldon syndrome (FSS), is the most severe DA syndrome. Patients with FSS have, in addition to distal joint contractures, facial findings secondary to contractures of facial muscles. A small mouth with a whistling-like appearance is a universal finding. The eyes are often deep-set and the nasal bridge wide. Other findings include epicanthal folds, strabismus, bilateral ptosis, and reduced eyelid size. FSS patients also often have H-shaped dimpling of the chin, small nose, long philtrum, high palate, small tongue, and nasal speech. Skeletal finding include ulnar deviation of the hands, camptodactyly, kyphoscoliosis, clubfoot, and contractures of the knees or hips. Distal arthrogryposis 2B (DA2B, OMIM 601680), or Sheldon-Hall syndrome (SHS) is the most common DA syndrome. Clinically, SHS is less severe than FSS but more severe than TPM2-related DA (DA1). Facial features reminiscent of FSS are present but are less pronounced.
Genetics
MYH3-associated distal arthrogryposis syndromes are inherited as autosomal dominant disorders. Missense variants affecting catalytic activity of the embryonic skeletal muscle myosin heavy chain protein are a known cause of FSS (Toydemir et al. Nat Genet 38:561-565, 2006; Tajsharghi et al. Arch Neurol 65:1083-1090, 2008). In contrast, variants in MYH3 which alter residues that interact with other proteins of the contractile apparatus, such as actin and troponin, have been shown to cause SHS (Toydemir et al. 2006). Thus far, with one exception, amino acid substitutions are the only form of MYH3 variants identified in patients. A single amino acid deletion represents the one exception, and this change was found in two unrelated SHS patients (Toydemir et al. 2006). SHS is also caused by variants in the TNNT3 and TNNI2 genes (Sung et al. Am J Hum Genet 73:212-4, 2003).
Clinical Sensitivity - Sequencing with CNV PGxome
MYH3 variants appear to be a common cause of Freeman-Sheldon syndrome. Variants were found in 26 of 28 cases, 75% of which were sporadic (Toydemir et al. 2006). Among 38 Sheldon-Hall syndrome patients who tested negative for variants in TNNI2 or TNNT3, 12 were found to have MYH3 variants.
Testing Strategy
This test provides full coverage of all coding exons of the MYH3 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 distal arthrogryposis and facial features consistent with Freeman-Sheldon or Sheldon-Hall syndromes.
Individuals with clinical symptoms consistent with distal arthrogryposis and facial features consistent with Freeman-Sheldon or Sheldon-Hall syndromes.
Gene
Official Gene Symbol | OMIM ID |
---|---|
MYH3 | 160720 |
Inheritance | Abbreviation |
---|---|
Autosomal Dominant | AD |
Autosomal Recessive | AR |
X-Linked | XL |
Mitochondrial | MT |
Diseases
Name | Inheritance | OMIM ID |
---|---|---|
Arthrogryposis, Distal, Type 2B | AD | 601680 |
Freeman-Sheldon Syndrome | AD | 193700 |
Citations
- Bamshad M. et al. 1996. American Journal of Medical Genetics. 65: 277-81. PubMed ID: 8923935
- Sung, S. S., et.al. (2003). "Mutations in TNNT3 cause multiple congenital contractures: a second locus for distal arthrogryposis type 2B." Am J Hum Genet 73(1): 212-4. PubMed ID: 12865991
- Tajsharghi, H., et.al. (2008). "Embryonic myosin heavy-chain mutations cause distal arthrogryposis and developmental myosin myopathy that persists postnatally." Arch Neurol 65(8): 1083-90. PubMed ID: 18695058
- Toydemir R.M. et al. 2006. Nature Genetics. 38: 561-5. PubMed ID: 16642020
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
STAT and Prenatal Test Options are not available with Patient Plus.
No Additional Test Options are available for this test.