Maturity-Onset Diabetes of the Young (MODY) Genetic Profile

CPT: 81404; 81405(x2); 81406(x2)
Updated on 10/14/2019
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Test Includes

This profile detects pathogenic variants and copy number variants in the coding sequence and exon-intron junctions of the four genes most commonly involved in MODY: HNF1A, GCK, HNF4A, and HNF1B.


Special Instructions

A Clinical Questionnaire for Maturity-Onset Diabetes of the Young (MODY) should be submitted with specimens.

This assay is currently not available in New York.

This assay is currently not available in New York.

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This assay is currently not available in New York.

A Clinical Questionnaire for Maturity-Onset Diabetes of the Young (MODY) should be submitted with specimens.

>

This assay is currently not available in New York.



Specimen Requirements


Specimen

Whole blood


Volume

3.0 mL


Minimum Volume

1.0 mL


Container

Lavender-top (EDTA) tube


Storage Instructions

Room temperature


Stability Requirements

Temperature

Period

Room temperature

14 days

Refrigerated

14 days


Causes for Rejection

Improper specimens; frozen samples; hemolyzed samples


Test Details


Use

Maturity-onset diabetes of the young (MODY) is a suspected diagnosis in young non-obese patients who lack an autoimmune cause for diabetes and who have a family history of diabetes in successive generations. The majority of MODY cases are due to mutations in one of four genes. Identifying a mutation in one of these MODY genes can lead to improved treatment, increased surveillance for related symptoms, and earlier detection in currently asymptomatic family members. GCK encodes the enzyme glucokinase, a key regulator of glucose metabolism in pancreatic beta cells. The three HNF (hepatic nuclear factor) genes encode transcription factors that regulate gene expression in the pancreas.

Mody #

Gene

Chromosome Location

RefSeq (Gene)

Transcript

MODY 3

HNF1A

12q24.31

NG_011731.2

NM_000545.6

MODY 1

HNF4A

20q13.12

NG_009818.1

NM_175914.4

MODY 5

HNF1B

17q12

NG_013019.2

NM_000458.3

MODY 2

GCK

7p13

NG_008847.2

NM_000162.5


Limitations

Mutation analysis is performed using bidirectional Sanger sequencing of the exons and splice junctions for each gene analyzed. Copy number variants (CNVs) are detected by semi‐quantitative PCR. Analytical sensitivity is estimated to be >99% for single nucleotide variants and small insertions/deletions, while clinical sensitivity can vary with the selection criteria and is predicted to be at least 85%. Variant classification is consistent with ACMG standards and guidelines. A variant of uncertain significance (VUS) is a classification based on inadequate or conflicting evidence and should not be used in clinical decision making. This assay reports pathogenic or likely pathogenic mutations and VUS's, while benign or likely benign variants are not reported. Numbering and nomenclature use the recommendations of the Human Genome Variation Society (HGVS: http://www.hgvs.org) and the transcript versions listed above.

This analysis does not detect germline mosaicism, large chromosomal rearrangements that do not alter copy number, and regions or genes not included in this test. Variant classification and/or interpretation may change with time if more information becomes available. False positive or negative results may occur for reasons that include: genetic variants that affect the assay, blood transfusions, mosaicism, mislabeled samples, or erroneous representation of family relationships.


Methodology

Sanger sequencing and MLPA


References

Bellanne‐Chantelot C, Clauin S, Chauveau D, et al. Large genomic rearrangements in the hepatocyte nuclear factor‐1beta (TCF2) gene are the most frequent cause of maturity‐onset diabetes of the young type 5. Diabetes. 2005 Nov;54(11):3126-3132.16249435
Ellard S, Thomas K, Edghill EL, et al. Partial and whole gene deletion mutations of the GCK and HNF1A genes in maturity‐onset diabetes of the young. Diabetologia. 2007 Nov;50(11):2313-2317.17828387
Ellard S, Colclough K. Mutations in the genes encoding the transcription factors hepatocyte nuclear factor 1 alpha (HNF1A) and 4 alpha (HNF4A) in maturity-onset diabetes of the young. Hum Mutat. 2006 Sep;27(9):854-869.16917892
Gloyn AL. Glucokinase (GCK) mutations in hyper- and hypoglycemia: maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemia of infancy. Hum Mutat. 2003 Nov;22(5):353-362.14517946
Hattersley AT, Patel KA. Precision diabetes: learning from monogenic diabetes. Diabetologia. 2017 May;60(5):769-777.28314945
Osbak KK, Colclough K, Saint-Martin C, et al. Update on mutations in glucokinase (GCK), which cause maturity‐onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemic hypoglycemia. Hum Mutat. 2009 Nov;30(11):1512-1526.19790256

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