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Test Code HNF1A KN HNF1A Known

Clinical System Name

HNF1A Known Mutation Analysis

Synonyms

MODY3

Description

This test involves targeted analysis for mutations previously identified through clinical testing of a family member or  research testing of the individual.  For full gene sequencing please see HNF1A Sequencing.

 

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.
 

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

Sample Requirements

Specimen: Whole blood, cord blood

Container(s): Lavender/EDTA, Yellow/ACD A or B

Preferred Vol: 3 mL

Minimum Vol: 1 mL

 

Note: Heparin samples (Green tops) are unacceptable.

 

Specimen: Extracted DNA

Minimum: 10µg

Note: DNA concentration minimum 50 µg/mL; 260/280 ratio 1.70-2.00

  

Specimen: Cultured cells

Acceptable:  Fibroblasts

Container(s): T-25 flasks

Preferred Vol: 2 flasks

 

 

 

 

Processing Instructions

Reject due to: Heparin

Spin: No

Aliquot: No

Temp: Refrigerate

Storage location: Molecular Genetics box in CPA refrigerator #2

 

Off-site collection: Refrigerate blood samples until ready to ship.  Transport all sample types at room temperature via overnight shipping.

Stability

Specimen Type Temperature Time
Cultured cells Room temp 3 days
Whole blood, extracted DNA Room temp 3-5 days
Whole blood, extracted DNA Refrigerated 7 days
Extracted DNA Frozen ok

 

Note: Whole blood samples > 7days may be submitted to be assessed by our lab for acceptability for testing.

Availability

STAT Performed TAT
Contact lab Monday - Friday 2-3 weeks

 

Performing Laboratory

Seattle Children's Laboratory

Department

Department:  Molecular Genetics Laboratory

Phone: 206-987-3872

 

Lab Client Services: 206-987-2617

 

Lab Genetic Counselors: LabGC@seattlechildrens.org

Reference Range

Interpretive report will be provided

Methodology

Method: PCR + Sequencing

 

Limitations: This test is for targeted known mutation analysis only.  Mutation(s) must be known.

CPT Codes

81403 (updated 1/19/16 jconta)

Special Instructions

Please provide copies of proband reports when requesting known mutation analysis for cases NOT performed by Seattle Children's Lab.

 

 

Links to: DiabetesGenes.org

Requisition

Molecular Genetics

Clinical Utility

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.
 



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.