Majeed Syndrome via the LPIN2 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 | |
|---|---|---|---|---|---|
| 11453 | LPIN2 | 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
Majeed Syndrome (MS) is diagnosed based on a triad of clinical findings including chronic recurrent multifocal osteomyelitis (CRMO), dyserythropoietic anemia, and inflammatory dermatosis. CRMO onset occurs before two years of age with 1-3 bouts per month lasting a few days. High fever, severe pain, and periarticular tender soft tissue swelling involving large joints are common symptoms during CRMO. Other symptoms may also include neutropenia, hepatomegaly, transient cholestatic jaundice, growth retardation, chronic anemia, and development of permanent flexion contractures. Genetic testing is helpful in confirming diagnosis of MS and for differential diagnosis from other hereditary periodic fevers, congenital dyserythropoietic anemia and sporadic forms of CRMO (Caso et al. 2013). MS is a very rare disorder affecting less than 1 per million individuals (El-Shanti and Ferguson 2013).
Genetics
MS is a fully penetrant disorder that is inherited in an autosomal recessive manner through mutations in the LPIN2 gene. To date, only four families have been reported to have MS with nonsense and small deletion mutations leading to frame shift and premature protein termination being most prevalent. In one case, a missense mutation was identified to cause MS (El-Shanti and Ferguson 2013; Ferguson et al. 2005). No gross deletions have been reported to date (Touitou et al. 2004). Lipin-2 is a member of the lipin enzyme family and facilitates biosynthesis of lipids. Lipin-2 serves as a protective role in regulating inflammation as deletion of the gene leads to enhanced expression of pro-inflammatory cytokines including IL-6, CCL2, and TNF alpha (Valdearcos et al. 2012).
Clinical Sensitivity - Sequencing with CNV PGxome
Analytical sensitivity should be high because all mutations reported are detectable by sequencing. Clinical sensitivity cannot be estimated because only a small number of cases have been reported.
No gross deletions have been reported in literature.
Testing Strategy
This test provides full coverage of all coding exons of the LPIN2 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 features consistent with Majeed Syndrome and laboratory findings showing elevated C-reactive protein and erythrocyte sedimentation rates are ideal candidates for testing (El-Shanti and Ferguson 2013). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in LPIN2.
Individuals with clinical features consistent with Majeed Syndrome and laboratory findings showing elevated C-reactive protein and erythrocyte sedimentation rates are ideal candidates for testing (El-Shanti and Ferguson 2013). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in LPIN2.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| LPIN2 | 605519 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Majeed Syndrome | AR | 609628 |
Citations
- Caso F, Rigante D, Vitale A, Lucherini OM, Costa L, Atteno M, Compagnone A, Caso P, Frediani B, Galeazzi M, Punzi L, Cantarini L. 2013. Monogenic Autoinflammatory Syndromes: State of the Art on Genetic, Clinical, and Therapeutic Issues. International Journal of Rheumatology 2013: 1–15. PubMed ID: 24282415
- El-Shanti H, Ferguson P. 2013. Majeed Syndrome. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301735
- Ferguson PJ. 2005. Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia (Majeed syndrome). Journal of Medical Genetics 42: 551–557. PubMed ID: 15994876
- Touitou I, Lesage S, McDermott M, Cuisset L, Hoffman H, Dode C, Shoham N, Aganna E, Hugot J-P, Wise C, Waterham H, Pugnere D, Demaille J, Sarrauste de Menthiere C. 2004. Infevers: An evolving mutation database for auto-inflammatory syndromes. Human Mutation 24: 194–198. PubMed ID: 15300846
- Valdearcos M, Esquinas E, Meana C, Pena L, Gil-de-Gomez L, Balsinde J, Balboa MA. 2012. Lipin-2 Reduces Proinflammatory Signaling Induced by Saturated Fatty Acids in Macrophages. J Biol Chem 287: 10894–10904. PubMed ID: 22334674
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
Loading...
×
ORDER OPTIONS
View Ordering Instructions1) Select Test Type
2) Select Additional Test Options
No Additional Test Options are available for this test.