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HelpTest Code LAB1885 Neonatal Diabetes Panel
Clinical System Name
Neonatal Diabetes Sequencing
Description
Neonatal diabetes mellitus (NDM) is a defect of insulin production characterized by the onset of hyperglycemia in the first six months of life. About half of NDM cases are classified as transient neonatal diabetes mellitus (TNDM), in which the condition disappears during infancy but can reappear later in life. The remaining cases are life-long and are called permanent neonatal diabetes mellitus (PNDM).
The Neonatal Diabetes panel includes DNA sequencing of these genes: ABCC8, EIF2AK3, FOXP3, GATA4, GATA6, GCK, GLIS3, HNF1B, IER3IP1, INS, INS-IGF2, KCNJ11, MNX1, NEUROD1, NEUROG3, NKX2-2, PDX1, PTF1A, RFX6, SLC19A2, SLC2A2, WFS1, ZFP57
Testing is appropriate for:
- Infants with persistent hyperglycemia ± history of intrauterine growth retardation, osmotic polyuria, severe dehydration and failure to thrive.
- Older individuals with history of the above symptoms
- Infants with hyperinsulinism
Targeted gene and targeted variant testing are also available for the genes in our panel. Targeted analysis for sequence variants previously identified through clinical testing of a family member or research testing of the individual. Please provide copies of proband reports when requesting known mutation analysis for cases NOT performed by Seattle Children's Lab.
Sample Requirements
Note: For patients who have had a whole blood transfusion, wait 10 days post transfusion to draw for genetic testing. No wait time is necessary for blood or saliva collection if the patient received leuko-reduced red cells or plasma.
Specimen: Whole blood
Container(s): Lavender/EDTA
Preferred Vol: 3 mL
Minimum Vol: 1 mL
Specimen: Saliva collected using Oragene Dx OGD-575/675 collection kit.
Container: Oragene Dx OGD-575/675 collection kit
IMPORTANT NOTE: Manufacturer instructions must be followed. The Oragene Dx OGD575/675 kit is not for children under 6 months. Contact the lab directly for more information or to obtain a kit - 206-987-2617
Specimen: Extracted DNA (MUST specify source on requisition)
Preferred: 10µg
Minimum: 5µg
Note: Isolation of nucleic acids for clinical testing must be performed in a CLIA-certified
laboratory or a laboratory meeting equivalent requirements as determined by the CAP
and/or the CMS. DNA concentration minimum 50 µg/mL; 260/280 ratio 1.70-2.00.
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 |
|---|---|---|
| Whole blood, extracted DNA | Room temp | 3-5 days |
| Whole blood, extracted DNA | Refrigerated | 7 days |
|
Saliva, extracted from ORAgene Dx OGD-575/675 |
Room temp or refrigerated | up to 2 weeks |
| Extracted DNA | Frozen | years |
Note: Whole blood samples >7 days may be submitted to be assessed by our lab for acceptability for testing.
Availability
| STAT | Performed | TAT |
|---|---|---|
| Contact lab | Monday - Friday | 4-6 weeks |
Performing Laboratory
Seattle Children's Laboratory
Department
Department: Molecular Genetics Laboratory
Phone: 206-987-3872
Lab Client Services: 206-987-2617
Lab Genetic Counselor: LabGC@seattlechildrens.org
CPT Codes
Neonatal Diabetes Panel: 81479
Call or email Lab Client Services, (206-987-2617 or labclientservices@seattlechildrens.org) for price and CPT information.
Methodology
Method: Next Generation Sequencing technology using an Illumina NextSeq instrument. Target region includes coding exons and a minimum of 10 bp of flanking intron boundaries of the genes tested. Target enrichment performed using a custom Integrated DNA Technologies (IDT) Exome Hyb Panel v2.
Average coverage ~150x, depth of coverage for all target regions is at least 20x.
Reported gene set: ABCC8, EIF2AK3, FOXP3, GATA4, GATA6, GCK, GLIS3, HNF1B, IER3IP1, INS, INS-IGF2, KCNJ11, MNX1, NEUROD1, NEUROG3, NKX2-2, PDX1, PTF1A, RFX6, SLC19A2, SLC2A2, WFS1, ZFP57
Limitations:
This testing is performed on an exome backbone with analysis restricted to the panel genes. This method can detect single nucleotide variants (SNVs), small deletions, small insertions, and copy number variants in the regions targeted. Some regions cannot be efficiently captured due to sequence homology or sequence properties. This method will not detect large insertions and deletions, complex indels, structural variants (e.g. inversions, translocations), short tandem repeats, or other complex variants. Variants located outside of targeted regions will not be detected.
Based on validation studies, the bioinformatics pipeline showed precision and detection >99% for SNVs in regions with coverage greater than 20x and high mapping quality. Sensitivity for CNVs involving multiple genes is >99% and sensitivity for intragenic CNVs is >90%. Mosaic sequence variants present at <25% allele frequency may not be reliably detected, and detection sensitivity is dependent on the nature of the variant. The sensitivity of detection of mosaic copy number variants has not been evaluated.
Reference Range
Interpretive report will be provided. Variants are not reported if they are considered benign.
Special Instructions
Links to: Permanent Neonatal Diabetes Mellitus Gene Review; DiabetesGenes.org
Requisition
Clinical Utility
Clinical features of NDM include intrauterine growth retardation, hyperglycemia, glycosuria, osmotic polyuria, severe dehydration, and failure to thrive. It is a rare condition occurring in one of 100,000 to 500,000 live births. About half of NDM cases are classified as transient neonatal diabetes mellitus (TNDM), in which the condition disappears during infancy but can reappear later in life. The remaining cases are life-long and are called permanent neonatal diabetes mellitus (PNDM). Management may be tailored depending on the specific mutations. For example, those with KCNJ11 and ABCC8 mutations can be successfully treated with oral sulfonylureas instead of insulin.