MFN2-Related Disorders via the MFN2 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 | |
|---|---|---|---|---|---|
| 11469 | MFN2 | 81406 | 81406,81479 | $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
The primary disease caused by MFN2 mutations is Charcot-Marie-Tooth disease 2A (CMT2A), which is an axonal form of hereditary motor and sensory neuropathies (HMSN). CMT2A patients have a normal or slightly reduced nerve conduction velocity (NCV) (Züchner et al. 2004; Calvo et al. 2009). A wide clinical variability exists from mild forms to early-onset severe forms. Less frequently reported, MFN2 mutations have also been associated with mitochondrial DNA instability (mitochondrial DNA depletion or deletions syndrome) (Renaldo et al. 2012; Rouzier et al. 2012; Vielhaber et al. 2013). Patients can have an early-onset progressive multisystemic disorder with mitochondrial DNA depletion in skeletal muscle, or an early-onset autosomal dominant optic atrophy ‘plus’ phenotype with mitochondrial DNA deletions.
Genetics
Most MFN2-related CMT cases are caused by either dominantly transmitted or de novo mutations (Züchner et al. 2004; Calvo et al. 2009). Recessive inheritance has also been reported, but is rare. MFN2-related mitochondrial DNA instability diseases are caused by heterozygous MFN2 mutations (Renaldo et al. 2012; Rouzier et al. 2012; Vielhaber et al. 2013). MFN2 has 17 coding exons that encode the mitochondrial GTPase mitofusin 2, which is involved in the fusion of the mitochondrial membrane. Missense (the vast majority), nonsense, splicing site mutations, and small deletion/insertions have been found over the whole coding region of MFN2. A large intragenic deletion has also been reported (Human Gene Mutation Database).
Clinical Sensitivity - Sequencing with CNV PGxome
In a group of 107 patients with CMT2, 19 (17.8%) were found to have heterozygous MFN2 mutations (Calvo et al. 2009). In another study of 85 Spanish families with axonal CMT, MFN2 mutations were identified in 16% of the total cohort (Casasnovas et al. 2010). Mutation detection rate of the MFN2 gene in a larger cohort of patients with a mitochondrial DNA instability disease is unavailable in the literature. Documented MFN2 mutations have been reported only in individual cases.
Testing Strategy
This test provides full coverage of all coding exons of the MFN2 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 patients with an axonal form of hereditary motor and sensory neuropathies (HMSN) or a mitochondrial DNA instability disease. Testing is also indicated for family members of patients who have known MFN2 mutations. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in MFN2.
Candidates for this test are patients with an axonal form of hereditary motor and sensory neuropathies (HMSN) or a mitochondrial DNA instability disease. Testing is also indicated for family members of patients who have known MFN2 mutations. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in MFN2.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| MFN2 | 608507 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Diseases
| Name | Inheritance | OMIM ID |
|---|---|---|
| Charcot-Marie-Tooth disease, axonal, type 2A2B | AR | 617087 |
| Charcot-Marie-Tooth Disease, Type 2A2 | AD | 609260 |
| Neuropathy, Hereditary Motor and Sensory, Type VIA | AD | 601152 |
Citations
- Calvo J, Funalot B, Ouvrier RA, Lazaro L, Toutain A, Mas P De, Bouche P, Gilbert-Dussardier B, Arne-Bes M-C, Carrière J-P, Journel H, Minot-Myhie M-C, et al. 2009. Genotype-phenotype correlations in Charcot-Marie-Tooth disease type 2 caused by mitofusin 2 mutations. Arch. Neurol. 66: 1511-1516. PubMed ID: 20008656
- Casasnovas C, Banchs I, Cassereau J, Gueguen N, Chevrollier A, Martínez-Matos JA, Bonneau D, Volpini V. 2010. Phenotypic spectrum of MFN2 mutations in the Spanish population. J. Med. Genet. 47: 249-256. PubMed ID: 19889647
- Human Gene Mutation Database (Bio-base).
- Renaldo F, Amati-Bonneau P, Slama A, Romana C, Forin V, Doummar D, Barnerias C, Bursztyn J, Mayer M, Khouri N, Billette de Villemeur T, Burglen L, et al. 2012. MFN2, a new gene responsible for mitochondrial DNA depletion. Brain 135: e223, 1-4; author reply e224, 1-3. PubMed ID: 22556188
- Rouzier C, Bannwarth S, Chaussenot A, Chevrollier A, Verschueren A, Bonello-Palot N, Fragaki K, Cano A, Pouget J, Pellissier J-F, Procaccio V, Chabrol B, et al. 2012. The MFN2 gene is responsible for mitochondrial DNA instability and optic atrophy “plus” phenotype. Brain 135: 23-34. PubMed ID: 22189565
- Vielhaber S, Debska-Vielhaber G, Peeva V, Schoeler S, Kudin AP, Minin I, Schreiber S, Dengler R, Kollewe K, Zuschratter W, Kornblum C, Zsurka G, et al. 2013. Mitofusin 2 mutations affect mitochondrial function by mitochondrial DNA depletion. Acta Neuropathol. 125: 245-256. PubMed ID: 22926664
- Züchner S, Mersiyanova IV, Muglia M, Bissar-Tadmouri N, Rochelle J, Dadali EL, Zappia M, Nelis E, Patitucci A, Senderek J, Parman Y, Evgrafov O, et al. 2004. Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A. Nat. Genet. 36: 449-451. PubMed ID: 15064763
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
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2) Select Additional Test Options
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