Monogenic Diabetes Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
4303 ABCC8 81407,81479 Order Options and Pricing
AIRE 81406,81479
AKT2 81479,81479
ALMS1 81479,81479
APPL1 81479,81479
BLK 81479,81479
CISD2 81479,81479
CNOT1 81479,81479
CP 81479,81479
DCAF17 81479,81479
DNAJC3 81479,81479
DYRK1B 81479,81479
EIF2AK3 81479,81479
EIF2B1 81479,81479
EIF2S3 81479,81479
FOXP3 81479,81479
GATA4 81479,81479
GATA6 81479,81479
GCK 81406,81479
GLIS3 81479,81479
HNF1A 81405,81479
HNF1B 81405,81404
HNF4A 81406,81479
IER3IP1 81479,81479
IL2RA 81479,81479
INS 81404,81479
INSR 81479,81479
ITCH 81479,81479
KCNJ11 81403,81479
KLF11 81479,81479
LRBA 81479,81479
MAFA 81479,81479
NEUROD1 81479,81479
NEUROG3 81479,81479
NKX2-2 81479,81479
PAX4 81479,81479
PAX6 81479,81479
PCBD1 81479,81479
PDX1 81404,81479
PIK3R1 81479,81479
POLD1 81479,81479
PPP1R15B 81479,81479
PTF1A 81479,81479
RFX6 81479,81479
SLC19A2 81479,81479
SLC29A3 81479,81479
SLC2A2 81479,81479
STAT1 81479,81479
STAT3 81479,81479
TRMT10A 81479,81479
WFS1 81479,81479
ZBTB20 81479,81479
ZFP57 81479,81479
ZMPSTE24 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
4303Genes x (54)81479 81403, 81404, 81405, 81406, 81407, 81479 $1090 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

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).

Genetics

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).

Testing Strategy

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.

Diseases

Name Inheritance OMIM ID
Abdominal obesity-metabolic syndrome 3 AD 615812
Aceruloplasminemia AR 604290
Agammaglobulinemia 7, Autosomal Recessive AR 615214
Alstrom Syndrome AR 203800
Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus AR 616192
Atrial Septal Defect 2 AD 607941
Atrial septal defect 9 AD 614475
Atrioventricular Septal Defect 4 AD 614430
Atrioventricular septal defect 5 AD 614474
Autoimmune Disease, Multisystem, Infantile-Onset, 1 AD 615952
Autoimmune Disease, Syndromic Multisystem AR 613385
BH4-Deficient Hyperphenylalaninemia D AR 264070
Candidiasis, Familial, 7 AD 614162
Cataract 41 AD 116400
Coloboma Of Optic Disc AD 120430
Coloboma, Ocular AD 120200
Colorectal cancer, susceptibility to, 10 AD 612591
Congenital Aniridia AD 106210
Conotruncal Heart Malformations 217095
Deafness, Autosomal Dominant 6 AD 600965
Diabetes Mellitus And Insipidus With Optic Atrophy And Deafness AR 222300
Diabetes Mellitus Type 1 AR 222100
Diabetes Mellitus, Insulin-Dependent, 10 601942
Diabetes Mellitus, Insulin-Dependent, 2 AD 125852
Diabetes Mellitus, Insulin-Dependent, 20 612520
Diabetes Mellitus, Ketosis-Prone AD 612227
Diabetes Mellitus, Neonatal, With Congenital Hypothyroidism AR 610199
Diabetes Mellitus, Noninsulin-Dependent AD 125853
Diabetes mellitus, permanent neonatal AD 618858
Diabetes mellitus, permanent neonatal 3, with or without neurologic features AD 618857
Diabetes Mellitus, Permanent Neonatal, With Cerebellar Agenesis AR 609069
Diabetes, permanent neonatal 2, with or without neurologic features AD 618856
Diarrhea 4, Malabsorptive, Congenital AR 610370
Fallot Tetralogy AD 187500
Fanconi renotubular syndrome 4, with maturity-onset diabetes of the young AD 616026
Fanconi-Bickel Syndrome AR 227810
Foveal Hypoplasia And Presenile Cataract Syndrome AD 136520
Hepatic Adenomas, Familial 142330
Histiocytosis-lymphadenopathy plus syndrome AR 602782
Holoprosencephaly 12, with or without pancreatic agenesis AD 618500
Hyperimmunoglobulin E Syndrome AD 147060
Hyperinsulinemic Hypoglycemia Familial 5 AD 609968
Hyperinsulinemic Hypoglycemia, Familial 3 AD 602485
Hyperinsulinemic Hypoglycemia, Familial, 1 AD 256450
Hyperinsulinemic Hypoglycemia, Familial, 2 AD 601820
Hyperproinsulinemia AD 616214
Hypoglycemia, Neonatal, Simulating Foetopathia Diabetica AD 240900
Immunodeficiency 31A, mycobacteriosis, autosomal dominant AD 614892
Immunodeficiency 36 AD 616005
Immunodeficiency, Common Variable, 8, with Autoimmunity AR 614700
Immunodysregulation, Polyendocrinopathy And Enteropathy X-Linked XL 304790
Insulin-Resistant Diabetes Mellitus And Acanthosis Nigricans 610549
Insulinomatosis and diabetes mellitus AD 147630
Interleukin 2 Receptor, Alpha, Deficiency Of AR 606367
Keratitis, Hereditary AD 148190
Leprechaunism Syndrome AR 246200
Leucine-Induced Hypoglycemia AD 240800
Leukoencephalopathy With Vanishing White Matter AR 603896
Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome AD 615381
Mandibuloacral Dysplasia With Type B Lipodystrophy AR 608612
Maturity-Onset Diabetes Of The Young, Type 1 AD 125850
Maturity-Onset Diabetes Of The Young, Type 10 AD 613370
Maturity-Onset Diabetes Of The Young, Type 11 AD 613375
Maturity-onset diabetes of the young, type 13 AD 616329
Maturity-Onset Diabetes Of The Young, Type 14 AD 616511
Maturity-Onset Diabetes Of The Young, Type 2 AD 125851
Maturity-Onset Diabetes Of The Young, Type 3 AD 600496
Maturity-Onset Diabetes Of The Young, Type 4 606392
Maturity-Onset Diabetes Of The Young, Type 5 AD 137920
Maturity-Onset Diabetes Of The Young, Type 6 606394
Maturity-Onset Diabetes Of The Young, Type 7 610508
Maturity-Onset Diabetes Of The Young, Type 9 612225
MEHMO Syndrome XL 300148
Microcephaly, Epilepsy, And Diabetes Syndrome AR 614231
Microcephaly, short stature, and impaired glucose metabolism 1 AR 616033
Microcephaly, short stature, and impaired glucose metabolism 2 AR 616817
Mitchell-Riley syndrome AR 615710
Mycobacterial And Viral Infections, Susceptibility To, Autosomal Recessive AR 613796
Optic Nerve Hypoplasia, Bilateral AD 165550
Pancreatic agenesis 2 AR 615935
Pancreatic agenesis and congenital heart defects AD 600001
Pancreatic Agenesis, Congenital AR 260370
Permanent Neonatal Diabetes Mellitus AR 606176
Peters Anomaly AD 604229
Pineal Hyperplasia And Diabetes Mellitus Syndrome AR 262190
Polyglandular Autoimmune Syndrome, Type 1 AD 240300
Primrose Syndrome AD 259050
Renal Cell Carcinoma, Nonpapillary 144700
Restrictive Dermopathy, Lethal AR 275210
SHORT syndrome AD 269880
Testicular Anomalies with or without Congenital Heart Disease AD 615542
Thiamine Responsive Megaloblastic Anemia Syndrome AR 249270
Transient Neonatal Diabetes Mellitus 1 AD 601410
Transient Neonatal Diabetes Mellitus 2 610374
Transient Neonatal Diabetes Mellitus 3 AD 610582
Ventricular Septal Defect 1 AD 614429
Vissers-Bodmer syndrome AD 619033
Wolcott-Rallison Dysplasia AR 226980
Wolfram Syndrome 2 AR 604928
Wolfram-Like Syndrome, Autosomal Dominant AD 614296
Woodhouse-Sakati Syndrome AR 241080

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Specimen Types

Specimen Requirements and Shipping Details

Disease Resources

Maturity onset diabetes of the young (MODY)

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