Maturity Onset Diabetes of the Young (MODY) Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10305 ABCC8 81407,81479 Order Options
APPL1 81479,81479
BLK 81479,81479
GCK 81406,81479
HNF1A 81405,81479
HNF1B 81405,81404
HNF4A 81406,81479
INS 81404,81479
KCNJ11 81403,81479
KLF11 81479,81479
NEUROD1 81479,81479
PAX4 81479,81479
PDX1 81404,81479
WFS1 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10305 Genes x (14) 81479 81403, 81404, 81405, 81406, 81407, 81479 $890 Order Options

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.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

Targeted Testing

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

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

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. As this non-insulin dependent type of diabetes is frequently misdiagnosed as type 1 or type 2 diabetes, a timely and accurate molecular diagnosis of MODY is essential to treatment decisions, prognosis, family screening and obstetric management of gestational diabetes (Ellard et al. 2008. PubMed ID: 18297260). MODY has been conventionally classified into 14 types in terms of the causative genes.

Genetics

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), kinase stimulating insulin synthesis and secretion (BLK), the enzyme carboxyl ester lipase (CEL), the ATP-sensitive potassium (KATP) channels (ABCC8 and KCNJ11) and a protein involved in glucose metabolism (APPL1). Our current MODY panel covers all of these genes except for CEL.

This panel also includes the WFS1 gene, which is known to be associated with Wolfram syndrome characterized by diabetes mellitus, optic atrophy, diabetes insipidus, and deafness. Increased evidence showed that recessive pathogenic WFS1 pathogenic variants can cause non-syndromic monogenic diabetes (Li et al. 2020. PubMed ID: 31658956; Zalloua et al. 2008. PubMed ID: 18806274). WFS1 encodes a transmembrane glycoprotein termed wolframin, which is required for the normal functioning of endoplasmic reticulum (ER).

Pathogenic variants in HNF1A, HNF4A, GCK and HNF1B genes account for over 80% of all known MODY cases while defects in other genes are rare causes of MODY (Owen. 2013. PubMed ID: 23760703). Genetic defects throughout the genes in this panel include missense and various truncating variants (nonsense, splicing variants and small deletion/insertions) (Human Gene Mutation Database). Exon-level large deletions or duplications have been found in these genes: HNF1A, HNF4A, HNF1B, GCK, INS, ABCC8 and WFS1 (Human Gene Mutation Database). De novo variants are not uncommon in MODY genes, especially in HNF1A, HNF4A, GCK and HNF1B (Stanik et al. 2014. PubMed ID: 24323243; Heidet et al. 2010. PubMed ID: 20378641).

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

Testing Strategy

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

This panel typically provides 99.5% 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.

Due to technical difficulties, the CEL gene is not included in this panel. Pathogenic variants in CEL account for only a very small fraction of MODY cases (Torsvik et al. 2010. PubMed ID: 19760265; Fjeld et al. 2015. PubMed ID: 25774637).

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

Clinical Sensitivity - Sequencing with CNV PGxome

Over 80% of all known Maturity Onset Diabetes of the Young (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 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 with non-syndromic non-autoimmune diabetes mellitus (~1.2%) (Zalloua et al. 2008. PubMed ID: 18806274).

Exon-level large deletions have been found in the HNF1A, HNF4A, HNF1B, GCK, INS, ABCC8 and WFS1 genes (Human Gene Mutation Database). However, our internal data suggests copy number variants are relatively uncommon in the genes of this panel.

Indications for Test

Candidates for this test are patients with MODY. This test especially aids in a differential diagnosis of similar phenotypes by analyzing multiple genes simultaneously.

Genes

Official Gene Symbol OMIM ID
ABCC8 600509
APPL1 604299
BLK 191305
GCK 138079
HNF1A 142410
HNF1B 189907
HNF4A 600281
INS 176730
KCNJ11 600937
KLF11 603301
NEUROD1 601724
PAX4 167413
PDX1 600733
WFS1 606201
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Bansal et al. 2017. PubMed ID: 29207974
  • Ellard et al. 2008. PubMed ID: 18297260
  • Fjeld et al. 2015. PubMed ID: 25774637
  • Heidet et al. 2010. PubMed ID: 20378641
  • Human Gene Mutation Database (Bio-base).
  • Li et al. 2020. PubMed ID: 31658956
  • McDonald and Ellard. 2013. PubMed ID: 23878349
  • Owen. 2013. PubMed ID: 23760703
  • Stanik et al. 2014. PubMed ID: 24323243
  • Torsvik et al. 2010. PubMed ID: 19760265
  • Zalloua et al. 2008. PubMed ID: 18806274

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

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2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

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