Background:
Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes that results from mutations of one of a group of genes which affect the insulin-producing ability of the pancreas. This condition is characterized by childhood to early onset of diabetes. This condition is inherited in an autosomal dominant manner.
Reasons for Referral:
- Molecular diagnosis for individuals with suspected forms of diabetes
- Carrier testing
Methodology:
Next generation sequencing will analyze the exons or coding regions of 22 Diabetes of Young-Maturity Onset-associated genes using Illumina NextSeq 500/550 technology. Samples are prepared using hybridization probes to enrich exonic regions. This assay does not assess regions of insufficient coverage, introns and promoter regions; pseudogenes; where the reference genome is inaccurate or contains gaps and insertions; and regions of high GC or polynucleotide repeats, but may contain variants that impact gene function.
Exon-level deletion/duplication analysis is performed by running the NGS data through the Genome Analysis Toolkit (GATK) Germline Copy Number Variation best practices pipeline from GATK, version 4.1.4.1. A Bayesian model was validated clinically in our lab. The model can detect copy changes at a resolution of three (3) or more probe targets (exons) for deletions and duplications in genes that do not have pseudogenes, and is not designed to detect low-level mosaicism or balanced alterations.
Diabetes of Young-Maturity Onset (22 genes):
ABCC8, AKT2, CISD2, CP, EIF2AK3, FOXP3, GATA6, GCK, GLIS3, HNF1A, HNF1B, HNF4A, IER3IP1, INS, KCNJ11, NEUROD1, NEUROG3, PDX1, PTF1A, RFX6, SLC2A2, WFS1
Specimen Requirements:
Blood: EDTA or ACD (Solution A or B):
- Adult: 5 mL
- Child: 5 mL
- Infant: 2-3 mL
Saliva: 2 ORAgene™ Saliva Collection Kits (OGR-500) used according to manufacturer instructions. Please contact KDL Client Services for a Saliva Collection Kit for patients that cannot provide a blood sample.
Assisted Saliva: 4 ORAgene™ Assisted Saliva Collection Kits (OGR-575) used according to manufacturer instructions. Please contact KDL Client Services for an Assisted Saliva Collection Kit for patients that cannot provide a blood sample.
Skin Fibroblast: Punch Biopsy (Cell cultures will be prepared at KDL and used for testing), or 2 T-25 confluent flasks.
DNA: 5-10µg at a minimum of 60-100ng/µL (DNA must be extracted in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or CMS)
Prenatal:
- Direct Amniotic Fluid (10-20mL)
- Direct CVS
- Direct POC
- Cultured Amniocytes (2 T-25 flasks)
- Cultured CVS (2 T-25 flasks)
- Cultured Fetal Tissue: Product of Conception (2 T-25 flasks)
- Cord Blood (1-2mL)
Notice Regarding Molecular Genetic Testing on CVS or Amniotic Fluid Specimens:
Maternal cell rule-out testing will be performed on all prenatal specimens received. Please provide maternal blood (or saliva) in addition to the fetal specimen. Additional charges apply for the maternal cell rule-out test.
For routine testing of blood and saliva (or DNA extracted from them), KDL does NOT accept samples from patients within two (2) weeks of a packed cell/platelet transfusion or within four (4) weeks of a whole blood transfusion. For extraordinary circumstances, where testing must be performed within the above windows, please contact our lab.
A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES. Please include detailed clinical information, including ethnicity, clinical history, and family history.
Test Performed (Days):
Weekly
Turn Around Time:
6-8 weeks
Shipment Sensitivity Requirements:
- Package and ship specimen to remain cold, but not frozen.
- Ship via overnight express, using the FedEx priority overnight label provided.
- Contact Client Services for shipping kits and instructions at (855) 535-1522.
References:
Additional Info: