AIFM1-Related Disorders via the AIFM1 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 | |
---|---|---|---|---|---|
9881 | AIFM1 | 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
Pathogenic variants in AIFM1 can result in a spectrum of disorders which include: Combined Oxidative Phosphorylation Deficiency 6 (X-linked mitochondrial encephalomyopathy), Cowchock Syndrome (Charcot-Marie-Tooth, X-linked recessive 4 CMTX4), and X-linked Deafness 5 (Auditory Neuropathy, X-linked AUNX1). To date, no symptomatic female carriers have been reported.
Pathogenic missense variants were reported in 14 patients from 4 Chinese families with childhood-onset auditory neuropathy and delayed peripheral sensory neuropathy presenting as extremity numbness, unsteadiness, and areflexia (Zong et al. 2015). In another recent study, whole exome sequencing revealed two additional missense variants in patients with cerebellar ataxia, auditory neuropathy, and axonal neuropathy (Zhu et al. 2015). The original family described with Cowchock syndrome (CMT4X), was found to have an AIFM1 variant segregating with disease (Rinaldi et al. 2012). This family presented with early childhood onset of a slowly progressive axonal sensorimotor neuropathy associated with deafness and cognitive impairment. Follow-up of this family 10 years later described the clinical features as including distal weakness, muscle atrophy, sensory loss, areflexia, pes cavus, and hammertoes. Thus far, the mitochondrial encephalomyopathy phenotype has only been described in three patients (Ghezzi et al. 2010; Ardissone et al. 2015). Ghezzi et al. described two male cousins with psychomotor delay in infancy and continued regression, seizures, areflexia, and muscle weakness and wasting. In another study, a 39 year-old male was diagnosed with a early-onset, slowly progressive mitochondrial disease (Ardissone et al. 2015). He presented with gait and limb ataxia, hearing loss, and cognitive impairment in childhood. Nerve conduction studies were consistent with an axonal sensory and motor neuropathy.
Genetics
AIFM1-related disorders are inherited in an X-linked recessive manner. To date, missense and one in-frame small deletion are the only pathogenic variants reported in AIFM1 (Human Gene Mutation Database).
The AIFM1 gene encodes apoptosis-inducing factor 1, which is a flavoprotein located in the mitochondrial intermembrane space. This protein functions as a caspase-independent programmed cell death effector. The AIFM1 protein also functions as an FAD-dependent NADH oxidoreductase and plays a role in oxidative phosphorylation, redox control, and respiratory chain activity in healthy cells.
Clinical Sensitivity - Sequencing with CNV PGxome
Clinical sensitivity cannot be estimated because only a small number of patients for each disorder have been reported. Analytical sensitivity should be high because all reported pathogenic variants are detectable by sequencing.
Thus far, no large deletions or duplications involving the AIFM1 gene have been reported.
Testing Strategy
This test provides full coverage of all coding exons of the AIFM1 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 AIFM1-related disorders are candidates for testing. Testing is also indicated for family members of patients who have known AIFM1 mutations.
Individuals with clinical symptoms consistent with AIFM1-related disorders are candidates for testing. Testing is also indicated for family members of patients who have known AIFM1 mutations.
Gene
Official Gene Symbol | OMIM ID |
---|---|
AIFM1 | 300169 |
Inheritance | Abbreviation |
---|---|
Autosomal Dominant | AD |
Autosomal Recessive | AR |
X-Linked | XL |
Mitochondrial | MT |
Diseases
Name | Inheritance | OMIM ID |
---|---|---|
Combined Oxidative Phosphorylation Deficiency 6 | XL | 300816 |
Cowchock Syndrome | XL | 310490 |
Deafness, X-Linked 5 | XL | 300614 |
Citations
- Ardissone A. et al. 2015. Neurology. 84: 2193-5. PubMed ID: 25934856
- Ghezzi D. et al. 2010. American Journal of Human Genetics. 86: 639-49. PubMed ID: 20362274
- Human Gene Mutation Database (Bio-base).
- Rinaldi C. et al. 2012. American Journal of Human Genetics. 91: 1095-102. PubMed ID: 23217327
- Zhu X. et al. 2015. Genetics in Medicine. 17: 774-81. PubMed ID: 25590979
- Zong L. et al. 2015. Journal of Medical Genetics. 52: 523-31. PubMed ID: 25986071
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.