Maturity-Onset Diabetes of the Young (MODY) NGS Panel

Turnaround Time

8 weeks

CPT Code(s)

81479

Cost

$2,500

Genes

• Maturity-Onset Diabetes of the Young (MODY)
• Familial hyperinsulinism
• Fanconi renotubular syndrome
• Diabetes mellitus
• Leucine-sensitive hypoglycemia of infancy

This panel consists of 14 genes that have been associated with maturity-onset diabetes of the young (MODY) and some forms of familial hyperinsulinism. Maturity-onset diabetes of the young, or MODY, typically presents in adolescents or young adults under the age of 25. The features of this condition are atypical for both type 1 and type 2 diabetes mellitus as MODY is not usually associated with obesity, acanthosis nigricans, or hyperecholesterolemia, and response to insulin use for hyperglycemia is limited. MODY has an estimated prevalence of 1 in 10,000 adults with approximately 1-2% of all diabetics having this form. Patients with pathogenic variants in the HNF1A and HNF4A genes sometimes experience a worsening of hyperglycemia over time and may eventually require insulin for treatment. However, many individuals with MODY only require oral medications, while others have a stable level of hyperglycemia and may not need treatment at all. MODY is inherited in an autosomal dominant pattern in the majority of cases, and familial hyperinsulinism often shows lower penetrance than MODY. Confirmation of pathogenic variants can assist with accurate diagnosis and treatment as well as testing for other at-risk family members.

Molecular testing is useful to confirm the diagnosis and to identify the disease-causing mutations within a family to allow for carrier testing.

Next Generation Sequencing

The current design of the maturity-onset diabetes of the young panel covers the coding region for all 14 genes and the flanking intronic sequences. This method allows for analysis of greater than 98% of the targeted sequence for the detection of nucleotide substitutions and small deletions and duplications. Large deletions and duplications will not be detected by this panel. Mutations and variants identified on the panel are confirmed with Sanger sequencing. All novel and apparently pathogenic changes are reported when found within the coding region as well as within 10 base pairs of each intron/exon boundary for each gene. Promoter and 3' untranslated sequences are not included in the current analysis. It should be noted that the current protocol is not specifically designed to detect copy number alterations and single exon deletions may require additional follow-up to determine whether or not they represent technical artifacts. Pathogenic variants in the HNF1A gene are identified in 30-65% of patients with MODY, and alterations in the GCK gene account for an additional 30-50% of cases. Changes in the HNF4A and HNF1B genes are responsible for at least 5% each with alterations in the remaining genes contributing to a small percentage of affected individuals. We recommend further array-based testing to more accurately address the concerns of dosage alterations. The Cytogenetic Laboratory at GGC offers a high resolution microarray.

The preferred sample type is 3-5 ml of peripheral blood collected in an EDTA (purple top) tube. Extracted DNA and saliva are also accepted for this test. Saliva samples must be submitted in an approved saliva kit. Contact the lab to receive a saliva kit or to have one sent to your patient.

The specimen should be kept at room temperature and delivered via overnight shipping. If shipment is delayed by one or two days, the specimen should be refrigerated and shipped at room temperature. Do not freeze the specimen. Samples collected on Friday can be safely designated for Monday delivery.