Sign in →

Test Code HNF4A KN HNF4A Known

Clinical System Name

HNF4A Known Mutation Analysis

Synonyms

MODY1

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 HNF4A Sequencing.

 

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.

 

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.
 

HNF4A sequencing can be performed individually or as part of the MODY panel which includes sequencing for: MODY types 1, 2, and 3.

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.