Monogenic Diabetes Panel
Summary and Pricing
Test MethodExome Sequencing with CNV Detection
|Test Code||Test Copy Genes||Gene CPT Codes Copy CPT Codes|
|4303||ABCC8||81407,81479||Order Options and Pricing|
|Test Code||Test Copy Genes||Panel CPT Code||Gene CPT Codes Copy CPT Code||Base Price|
|4303||Genes x (54)||81479||81403, 81404, 81405, 81406, 81407, 81479||$1090||Order Options and Pricing|
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.
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.
For ordering sequencing of targeted known variants, go to our Targeted Variants page.
Clinical Features and Genetics
Monogenic diabetes is a clinically and genetically heterogeneous group of disorders due to pathogenic variants in a single gene, accounting for approximately 2% of people with diabetes (Harris et al. 2018. PubMed ID: 29846255). Monogenic diabetes includes maturity-onset diabetes of the young (MODY) and neonatal diabetes mellitus (NDM), as well as rarer syndromic diabetes such as monogenic forms of autoimmunity. Genetic testing for monogenic diabetes is critical for personalized treatment, since many patients can be misdiagnosed with type 1 or type 2 diabetes.
Maturity onset diabetes of the young (MODY), a primary pancreatic beta-cell defect, is the most common type of monogenic diabetes, accounting for up to 5% of young adults diagnosed with diabetes (Owen. 2013. PubMed ID: 23760703; McDonald and Ellard. 2013. PubMed ID: 23878349). MODY typically presents in lean young adults before 25 years with an autosomal dominant family history. MODY patients have continued production of endogenous insulin, absence of beta-cell autoimmunity, and absence of signs of insulin resistance. MODY has been conventionally classified into 14 types in terms of the causative genes.
Neonatal diabetes mellitus (NDM), also termed congenital diabetes or infancy-onset diabetes, has an estimated incidence of 1 out of 100,000 live births. It is typically diagnosed within the first six months of life (Harris et al. 2018. PubMed ID: 29846255). NDM consists of two forms: permanent and transient. The common symptoms of NDM include hyperglycemia, polyuria, tachypnea, tiredness, and dehydration. The transient form typically resolves by 18 months of age, while the permanent form requires lifelong treatment.
In diabetes occurring within 12 months of age, monogenic forms of autoimmunity-related diabetes are a subgroup that have positive pancreatic autoantibodies but are caused by defects in single genes. These monogenic autoimmune syndromes have highly variable phenotypes. Further investigation of these disorders may help discriminate them from type 1 diabetes and determine guidelines for genetic testing and treatment (Harris et al. 2018. PubMed ID: 29846255).
Monogenic diabetes is a clinically and genetically heterogeneous group of disorders that can be inherited in an autosomal dominant (including de novo), autosomal recessive, or X-linked manner. Causative variants include missense, nonsense, splicing, regulatory, and copy number alterations.
MODY is inherited in an autosomal dominant manner. Proteins encoded by MODY-associated genes include nuclear transcription factors controlling pancreatic development (HNF1A, HNF4A, HNF1B, PDX1, KLF11, PAX4, and NEUROD1); glucokinase, a glucose sensor in pancreatic beta-cells (GCK); insulin (INS); a kinase stimulating insulin synthesis and secretion (BLK); the enzyme carboxyl ester lipase (CEL); the ATP-sensitive potassium (KATP) channels (ABCC8 and KCNJ11); and glucose metabolism (APPL1).
For permanent neonatal diabetes mellitus (PNDM), dominant heterozygous pathogenic variants in KCNJ11 are the most common cause, followed by INS (dominant and recessive), ABCC8 (recessive), and GCK (recessive). Recessive variants in EIF2AK3, INS, and GCK are more common in consanguineous families (De Franco et al. 2015. PubMed ID: 26231457). For transient neonatal diabetes, 70% of cases have a methylation abnormality in the 6q24 region while pathogenic variants in other genes such as ABCC8, KCNJ11, INS, or HNF1B have also been reported (Harris et al. 2018. PubMed ID: 29846255).
The causative genes for diabetes-related monogenic forms of autoimmunity include FOXP3, IL2RA, LRBA, STAT1, and STAT3. Encoding a transcription factor (FOXP3), cell surface receptor (IL2RA), endosomal trafficking protein (LRBA), and STAT protein family members (STAT1 and STAT3), these genes play a vital role in maintaining the immune system (OMIM).
See individual gene summaries for information about molecular biology of gene products and spectra of pathogenic variants.
Clinical Sensitivity - Sequencing with CNV PGxome
Over 80% of all known MODY cases in the UK are caused by defects in HNF1A (~30%), HNF4A (~10%), GCK (~30%), or HNF1B (5-10%) (Owen. 2013. PubMed ID: 23760703). In the UK, HNF1A-MODY is the most common form in adults while GCK-MODY is the most common form in children.
In a large genomic screen study of 4,016 patients diagnosed with type 2 diabetes, nearly 2% of patients with early-onset (<40 years) disease were found to have pathogenic variants in MODY genes (Bansal et al. 2017. PubMed ID: 29207974).
In exome sequencing of 82 Chinese Han patients clinically diagnosed with type 1 diabetes but who were negative for three autoantibodies, 18 (~22%) patients were found to have plausibly pathogenic variants in MODY genes (14 cases; ~17%) or the WFS1 gene (4 cases; ~5%) (Li et al. 2020. PubMed ID: 31658956). In 399 probands with juvenile-onset diabetes in Lebanon, homozygous or compound heterozygous WFS1 variants were found in five patients (~1.25%) with non-syndromic non-autoimmune diabetes mellitus (Zalloua et al. 2008. PubMed ID: 18806274).
In a large international (79 countries) cohort study (1020 patients; 571 boys and 449 girls) of patients with neonatal diabetes diagnosed before six months of age, causal variants were identified in more than 80% of cases (De Franco et al. 2015. PubMed ID: 26231457).
This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.
This panel typically provides 99.8% 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 Custom Panels).
Indications for Test
Candidates for this test are patients with monogenic diabetes.
Candidates for this test are patients with monogenic diabetes.
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.
- 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.
Maturity onset diabetes of the young (MODY)