Mendelian Susceptibility to Mycobacterial Disease Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
13071 CARMIL2 81479,81479 Order Options and Pricing
CYBB 81479,81479
GATA2 81479,81479
IFNGR1 81479,81479
IFNGR2 81479,81479
IKBKG 81479,81479
IL12B 81479,81479
IL12RB1 81479,81479
IRAK4 81479,81479
IRF8 81479,81479
ISG15 81479,81479
JAK1 81479,81479
NFKBIA 81479,81479
RORC 81479,81479
SPPL2A 81479,81479
STAT1 81479,81479
TYK2 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
13071Genes x (17)81479 81479 $930 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare immunodeficiency syndrome with susceptibility to mycobacteria, such as environmental mycobacteria or the vaccine against tuberculosis [bacillus Calmette-Guérin (BCG)]. Individuals are typically resistant to infection with most other bacteria, fungi, viruses and parasites; however those with severe forms of disease may also be susceptible to these other pathogens (Qu et al. 2011. PubMed ID: 21330176; Bustamante et al. 2014. PubMed ID: 25453225). Beyond their susceptibility to weakly virulent mycobacteria, individuals with MSMD are typically healthy with no overt anomalies in routine hematological and immunological tests.

MSMD is characterized by severe, recurrent infections that may be disseminated or localized. There is significant allelic heterogeneity in the genes associated with MSMD and this is the reason for several different subtypes of MSMD. The most severe forms of MSMD develop in childhood and are characterized by serious, disseminated infections with mycobacteria that can affect the soft tissue, bone marrow, lungs, skin, bones and lymph nodes (Bustamante et al. 2014. PubMed ID: 25453225). Infections with other agents are often reported in those with early onset MSMD. More rarely, symptoms will develop during adolescence and adulthood and will usually be less severe. In addition, some genetically predisposed individuals may remain asymptomatic.

MSMD is a rare condition; its prevalence is not well established (Bustamante et al. 2014. PubMed ID: 25453225). There are many advantages of genetic testing for MSMD including informing treatment decisions such as antibiotic therapy, interferon gamma therapy, or hematopoietic stem cell transplantation, preventative measures such as avoidance of the BCG vaccine, and reproductive planning.

Genetics

This test includes genes identified through literature, OMIM, and HGMD searches that have a reported association with MSMD.

MSMD are heterogeneous disorders that may be inherited in an autosomal dominant (AD), autosomal recessive (AR), and X-linked (XL) manner, with some genes having more than one mode of inheritance. In addition, MSMD variants may arise de novo. Causative variants may include missense, nonsense, splicing, regulatory, or copy number alterations (Qu et al. 2011. PubMed ID: 21330176).

The products of the genes in this panel are involved in cytokine and interleukin signaling and regulation, hematopoiesis, and activation of the innate and/or adaptive immune response (Stasia and Li. 2008. PubMed ID: 18509647; Picard et al. 2010. PubMed ID: 21057262; Qu et al. 2011. PubMed ID: 21330176; Bustamante et al. 2014. PubMed ID: 25453225; Kreins et al. 2015. PubMed ID: 26304966; Okada et al. 2015. PubMed ID: 26160376; Boisson et al. 2017. PubMed ID: 28597146; Alazami et al. 2018. PubMed ID: 29479355; Donadieu et al. 2018. PubMed ID: 29724903; Gruber et al. 2020. PubMed ID: 32750333). Only about half of the individuals with MSMD have an identified genetic etiology. Subtypes are based upon several features including the impact of the variant, the mode of inheritance, the expression of the mutant allele, and the function affected (Bustamante et al. 2014. PubMed ID: 25453225).

Null variants in IFNGR1 and IFNGR2 are associated with severe forms of MSMD (Qu et al. 2011. PubMed ID: 21330176; Bustamante et al. 2011. PubMed ID: 21278736). Pathogenic variants in IKBKG (aka NEMO) and CYBB have been associated with X-linked forms of MSMD (Filipe-Santos et al. 2006. PubMed ID: 16818673; Qu et al. 2011. PubMed ID: 21330176; Bustamante et al. 2011. PubMed ID: 21278736). The other genetic causes of MSMD included in this panel have variable disease severity (however typically less severe than variants in IFNGR1 and IFNGR1) and inheritance patterns (Bousfiha et al. 2018. PubMed ID: 29226301; Picard et al. 2018. PubMed ID: 29226302; Tangye et al. 2020. PubMed ID: 31953710).

See the individual gene summaries for information about molecular biology of gene products and spectra of pathogenic variants.

Clinical Sensitivity - Sequencing with CNV PGxome

Due to the genetic heterogeneity and low incidence of MSMD, the clinical sensitivity of this specific grouping of genes is difficult to estimate. However, it has been estimated that the frequencies of variants in genes associated with MSMD is <1 per million and only about half of individuals with MSMD have an identified genetic etiology (Qu et al. 2011. PubMed ID: 21330176; Bustamante et al. 2014. PubMed ID: 25453225).

For their review, Bustamante compiled a cohort of 406 patients with MSMD (Bustamante et al. 2014. PubMed ID: 25453225). The breakdown in this cohort by gene for causative variants was IL12RB1 (44%), IFNGR1 (29%), IL12B (12%), and IFNGR2 (5%). Variants in CYBB, IRF8, ISG15, IKBKG (aka NEMO), and STAT1 were identified in 4% or less of the cohort.

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel typically provides 96.0% coverage of all coding exons of the genes 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 coverage as ≥20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome CustomPanels).

Indications for Test

Candidates for testing include individuals that present with susceptibility to mycobacteria. In addition, family members of those who have a susceptibility to mycobacteria may also be candidates for testing as some individuals may have a genetic predisposition but are asymptomatic or may be carriers.

Genes

Official Gene Symbol OMIM ID
CARMIL2 610859
CYBB 300481
GATA2 137295
IFNGR1 107470
IFNGR2 147569
IKBKG 300248
IL12B 161561
IL12RB1 601604
IRAK4 606883
IRF8 601565
ISG15 147571
JAK1 147795
NFKBIA 164008
RORC 602943
SPPL2A 608238
STAT1 600555
TYK2 176941
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Alazami et al. 2018. PubMed ID: 29479355
  • Boisson et al. 2017. PubMed ID: 28597146
  • Bousfiha et al. 2018. PubMed ID: 29226301
  • Bustamante et al. 2011. PubMed ID: 21278736
  • Bustamante et al. 2014. PubMed ID: 25453225
  • Donadieu et al. 2018. PubMed ID: 29724903
  • Filipe-Santos et al. 2006. PubMed ID: 16818673
  • Gruber et al. 2020. PubMed ID: 32750333
  • Kreins et al. 2015. PubMed ID: 26304966
  • Okada et al. 2015. PubMed ID: 26160376
  • Picard et al. 2010. PubMed ID: 21057262
  • Picard et al. 2018. PubMed ID: 29226302
  • Qu et al. 2011. PubMed ID: 21330176
  • Stasia and Li. 2008. PubMed ID: 18509647
  • Tangye et al. 2020. PubMed ID: 31953710

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.

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


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

1) 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.

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