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Diagnostic Services

Genetics Lab


Maturity-Onset Diabetes of the Young (MODY) Sequencing Panel

Maturity-Onset Diabetes of the Young (MODY) is an autosomal dominant form of diabetes typically occurring before age 25 and caused by a primary insulin secretion defect. MODY is not a single entity but represents nine classifications with genetic, metabolic, and clinical heterogeneity. MODY is estimated to affect approximately 1-2% of people with diabetes, although this may be an underestimate since the genetic etiology of this type of diabetes often goes undiagnosed.

Main features of MODY patients include the following: 1) Hyperglycemia usually diagnosed before age 25 years in at least 1 family member. 2) Autosomal dominant inheritance through at least 3 generations, and a phenotype shared by diabetic family members. 3) Absence of insulin therapy or significant C-peptide levels even in a patient on insulin treatment for several years after diagnosis.

The MODY panel tests for genetic mutations that cause MODY types 1, 2, and 3.

MODY 3 (HNF1A): This is the most common form of MODY, causing 60% of cases. It shares with MODY 1 the progressive hyperglycemia, risk for microvascular complications, and increasing need for treatment with sulfonylureas as the disease progresses. Approximately 1/3 of patients will ultimately require insulin to maintain euglycemia. Compared to MODY 1, patients with MODY 3 tend to have a lower renal threshold for glycosuria and a normal rather than reduced circulating lipoproteins and triglycerides, often with an elevated HDL. Despite the high HDL, the risk for coronary artery disease is increased in these patients.

MODY 2 (GCK): Approximately 25% of MODY is caused by mutations in the glucokinase (GCK) gene. It is associated with a mild form of nonprogressive hyperglycemia that is usually managed with diet alone. Individuals with GCK MODY rarely have overt symptoms of diabetes, and diabetes-associated complications are rare. These individuals are often diagnosed with diabetes or glucose intolerance on routine screening, particularly during pregnancy. Approximately 2-4% of gestational diabetes may be due to GCK mutations.

MODY 1 (HNF4A): Accounting for ~3% of MODY cases, MODY 1 is caused by mutations in the β-cell transcription factor gene, HNF4A. It has a similar presentation to MODY 3, including progressive hyperglycemia and microvascular complications. 30-40% of patients require sulfonylurea drugs or insulin over time.

Test Name: MODY Panel
Test Code:
Test Description:
Polymerase Chain Reaction (PCR) followed by sequence analysis of the entire coding region of each gene
HNF1A, HNF4A, GCK, hyperglycemia
GCK testing is indicated for individuals with the following clinical features:
1. Mild fasting hyperglycemia (100-145 mg/dl) that is stable over months to years
2. OGTT 2 hour glucose increment is usually <80 mg/dl
3. May have history of gestational diabetes that does not resolve post-partum
4. May have a family history of mild type 2 or gestational diabetes

HNF1A with reflex to HNF4A is indicated for individuals with the following clinical features:
1. Young onset diabetes (usually <25 years)
2. Prolonged non-insulin-requiring honeymoon period (>3 years) with evidence of residual beta-cell function:
a) Rare diabetic ketoacidosis
b) Good glycemic control on a small dose of insulin
c) Detectable C-peptide measured when on insulin

3. Large increment in blood glucose on OGTT (>80mg/dl), +/- normal fasting glucose
4. Strong, multigenerational family history of diabetes (may be diagnosed as either type 1 or 2 in different members)
5. Glycosuria at low levels of blood glucose
Related Tests:
Clinical Links: DiabetesGenes.Org (Peninsula Medical School, Exeter, UK)
Mon - Fri
Turnaround Time:
2-4 weeks
PCR followed by sequencing
Reference Range:
Interpretive report will be provided
Consent Form:
Sample Requirements: Type
Whole blood: 3-5 mL in EDTA (purple top) or ACD (yellow top).
DNA: 5 micrograms extracted DNA.

Do not spin. Keep at room temperature. Refrigerate samples which are not shipped immediately.

Room temperature via overnight shipping.
Samples Received:
Monday - Friday 8am - 5pm PST
Special Considerations:
Please e-mail Lab Client Services ( or call at 206-987-2617 with any billing questions
CPT Code:
Please e-mail Lab Client Services ( or call at 206-987-2617 with any billing questions