INS-Related Diabetes, Neonatal Diabetes (INS-Related)

Dominantly-inherited mutations in the insulin gene cause approximately 12% of permanent neonatal diabetes cases. Approximately 80% of mutations are de novo.  

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Dominantly-inherited mutations in the insulin gene cause approximately 12% of permanent neonatal diabetes cases. Approximately 80% of mutations are de novo.  

Patients may have reduced birthweight and most present within the first six months of life with ketoacidosis and marked hyperglycemia requiring a full replacement dose of insulin for maintenance therapy. Neurological or motor deficits are not known to be associated with the presence of insulin mutations. Insulin mutations have also been reported in a very small number of patients presenting with Type 1-like diabetes without autoantibodies, as MODY, or as younger-onset Type 2 diabetes.

Disease Name 
Neonatal Diabetes (INS-Related)
INS-Related Diabetes
Disease Information 

Dominantly-inherited mutations in the insulin gene cause approximately 12% of permanent neonatal diabetes cases.  Approximately 80% of mutations are de novo.  Patients may have reduced birthweight and most present within the first six months of life with ketoacidosis and marked hyperglycemia requiring a full replacement dose of insulin for maintenance therapy.  Neurological or motor deficits are not known to be associated with the presence of insulin mutations.  Insulin mutations have also been reported in a very small number of patients presenting with Type 1-like diabetes without autoantibodies, as MODY, or as younger-onset Type 2 diabetes.

Testing Benefits & Indication 

Diagnostic testing for individuals suspected to have neonatal diabetes; carrier testing for known familial mutations in INS.

Test Description 

The Ambry Test: INS-Related Diabetes includes gene sequence analysis of exons 1-3 plus at least 20 bases into the 5 and 3 ends of all the introns of the INS gene. The analyzed regions of the gene are amplified through polymerase chain reaction (PCR) and the exact nature of the genes sequence variation(s) can be identified through double-stranded sequencing from sense and anti-sense directions.  If specific mutation analysis is requested, only specific region(s) of DNA is (are) amplified by PCR and sequenced.

Mutation Detection Rate 

The Ambry Test: INS-Related Diabetes is designed and validated to be capable of detecting about 99% of described INS mutations (considering less than 1% to be the other types of mutations).

Specimen Requirements 

 

Blood Samples:
  • Container: Purple top EDTA tube (preferred) or yellow top citric acetate tube.
  • Amount: Adult 3-5 cc, pediatric 2 cc minimum.
  • Storage: 2-8°C. Do not freeze.
  • Shipment: Room temperature for two-day delivery.
     
  • Transfusion Patients: Wait at least two weeks after a packed cell or platelet transfusion and at least four weeks after a whole blood transfusion prior to blood draw.
DNA:
  • Container: Sterile plastic tube.
  • Amount: min. 20 μg of DNA in TE (10mM Tris-Cl pH 8.0, 1mM EDTA); preferred 200 μl at ~100 ng/μl.
  • For specific mutation(s) analysis: min. 5 μg of DNA (~100 ng/μl conc.).
  • Please provide DNA OD 260-280 ratio (preferred 1.7-1.9) and send agarose picture with high mw genomic DNA, if available.
  • Storage: -20°C.
  • Shipment: Shipment frozen on dry ice is preferred, or ship on ice.
     
  • For Transfusion Patients: Wait at least two weeks after a packed cell or platelet transfusion and at least four weeks after a whole blood transfusion prior to blood draw.
  • Blood Spots:
    • Container: Schleicher + Schuell (S&S) 903 specimen collection paper.
    • Amount: Minimum of one complete spot of approximately 0.5 inch in diameter.
    • Storage: Room temperature in a sterile bag.
    • Shipment: 2-8°C up to 72 hours. Do not freeze.
    • Availability: Please call for availability of testing on blood spots or see specimen requirements of specific test.
    • Blood spots not accepted for Ashkenazi Jewish FlexPanel, Gaucher (GBA), Hunter (IDS), Hurler (IDUA),
    • HNPCC (MLH1, MSH2, MSH6), CCHS (PHOX2B), PRSS1 (pancreatitis), Shwachman-Diamond (SBDS), Angelman-Like Syndrome,
    • (SLC9A6), or AAT Deficiency (SERPINA1) or Angelman/Prader-Willi Syndrome (UBE3A, SNRPN methylation).
    • Saliva:
      • Container: Oragene DNA Self Collection container.
      • Amount: 2 ml.
      • Storage: At room temperature in sterile bag.
      • Shipment: Ship room temperature for two-day delivery
         
Billing Codes 
Test Code Technique CPT Codes
1360 KCNJ11 Gene Sequence Analysis            83891x1, 83894x5, 83898x4, 83904x8, 83909x8, 83912x1
1620 INS Gene Sequence Analysis 83891x1, 83894x3, 83898x2, 83904x4, 83909x4, 83912x1

 

Turnaround Time 
Technique Days
KCNJ11 Gene Sequence Analysis            7-14
INS Gene Sequence Analysis                     7-14

 

Specialty 
Endocrinology
Genes 
INS
Techniques 
Gene Sequence Analysis
Specific Mutation Analysis
References 

References are available upon request.