MODY Panel - Clinical Genetic Test - GTR

Genetic Testing Registry

View Advanced Search Options

Classic view of this page

MODY Panel

Clinical Genetic Test

offered by

Genetic Services Laboratory

View lab's test page

GTR Test Accession: GTR000506425.7

CAP

INHERITED DISEASEDIGESTIVE SYSTEMENDOCRINOLOGY ... View more

Last updated in GTR: 2021-01-19

Last annual review date for the lab: 2024-07-22

At a Glance

Test purpose:

Diagnosis; Monitoring; Mutation Confirmation; ...

Conditions (10):

Maturity-onset diabetes of the young type 2; Maturity onset diabetes mellitus in young; Maturity-onset diabetes of the young type 10 more...

Genes (15):

ABCC8 (11p15.1); APPL1 (3p14.3); BLK (8p23.1); CEL (9q34.13); GCK (7p13) more...

Methods (2):

Molecular Genetics - Deletion/duplication analysis: Next-Generation (NGS)/Massively parallel sequencing (MPS); ...

Target population:

The target population for this test is patients suspected of …

Clinical validity:

Heterozygous inactivating GCK mutations are the most frequent monogenic cause …

Clinical utility:

Establish or confirm diagnosis

Ordering Information

Offered by:

Genetic Services Laboratory
View lab's website
View lab's test page

Specimen Source:

Buccal swab
Cell culture
Cord blood
Fetal blood
Fibroblasts
Peripheral (whole) blood
Saliva
View specimen requirements

Who can order:

Genetic Counselor
Health Care Provider
Licensed Physician
Nurse Practitioner
Physician Assistant
Registered Nurse

CPT codes:

81443

**AMA CPT codes notice

Contact Policy:

Laboratory can only accept contact from health care providers. Patients/families are encouraged to discuss genetic testing options with their health care provider.

How to Order:

All samples should be shipped via overnight delivery at room temperature.
No weekend or holiday deliveries.
Label each specimen with the patient’s name, date of birth and date sample collected.
Send specimens with complete requisition and consent form, otherwise, specimen processing may be delayed.
Order URL

Test service:

Clinical Testing/Confirmation of Mutations Identified Previously
Confirmation of research findings

Test additional service:

Custom Prenatal Testing
Custom mutation-specific/Carrier testing

Test development:

Test developed by laboratory but exempt from FDA oversight (eg. NYS CLEP approved, offered within a hospital or clinic)

Informed consent required:

Pre-test genetic counseling required:

Decline to answer

Post-test genetic counseling required:

Decline to answer

Recommended fields not provided:

Test Order Code, Lab contact for this test, Test strategy

Conditions

Total conditions: 10

Condition/Phenotype	Identifier

Test Targets

Genes

Total genes: 15

Gene	Associated Condition	Germline or Somatic	Allele (Lab-provided)	Variant in NCBI

Methodology

Total methods: 2

Method Category

Test method

Instrument *

Deletion/duplication analysis

Next-Generation (NGS)/Massively parallel sequencing (MPS)

Sequence analysis of the entire coding region

Next-Generation (NGS)/Massively parallel sequencing (MPS)

* Instrument: Not provided

Clinical Information

Test purpose:

Diagnosis; Monitoring; Mutation Confirmation; Pre-symptomatic; Risk Assessment; Screening

Clinical validity:

Heterozygous inactivating GCK mutations are the most frequent monogenic cause of diabetes in asymptomatic children with persistent hyperglycemia or glycosuria (MODY2). Mutations in the PDX1 gene are a rare cause of MODY. In a consanguineous family in which an infant with pancreatic agenesis was homozygous for a 1-bp deletion in … Heterozygous inactivating GCK mutations are the most frequent monogenic cause of diabetes in asymptomatic children with persistent hyperglycemia or glycosuria (MODY2). Mutations in the PDX1 gene are a rare cause of MODY. In a consanguineous family in which an infant with pancreatic agenesis was homozygous for a 1-bp deletion in the PDX1 gene, Stoffers et al. found that members heterozygous for this mutation had early-onset type 2 diabetes mellitus, which they designated MODY4 (OMIM#606392). The expression of diabetes in these families may occur at later ages than in families with other types of MODY. Heterozygous loss-of-function NEUROD1 mutations are a rare cause of MODY (OMIM# 606394). Diabetes mellitus caused by heterozygous mutations in NEUROD1 has been reported in three families and was subsequently designated as MODY6. More recently, two cases with neonatal diabetes by 2 months of age were described to exhibit cerebellar hypoplasia, developmental delay, sensorineural deafness, and visual impairment. They were found to carry two different homozygous frameshift mutations resulting in a truncated NEUROD1 protein. Heterozygous KLF11 point mutations are a rare cause of MODY (OMIM#610508). Heterozygous CEL frameshift deletions in the variable number of tandem repeats (VNTR) caused MODY (OMIM#609812) in two families with autosomal dominantly inherited diabetes and exocrine pancreas dysfunction. Heterozygous PAX4 mutations are a rare cause of MODY (OMIM#612225). Heterozygous INS mutations are a rare cause of MODY (OMIM#613370). Heterozygous BLK mutations are a rare cause of MODY (OMIM#613375). Recently, Johansson et al. identified a missense mutation in a patient with diabetes diagnosed at 25 years of age MODY patients suggesting that mutations in these genes can be associated with a large spectrum of diabetes phenotypes and can be not totally penetrant. Heterozygous KCNJ11 mutations have been recently identified by Bonnefond et al. in a patient with MODY confirming the wide spectrum of diabetes related phenotypes due to mutations in KCNJ11. View more

View citations (16)

Mutations in NEUROD1 are associated with the development of type 2 diabetes mellitus. Malecki MT, et al. Nat Genet. 1999;23(3):323-8. doi:10.1038/15500. PMID: 10545951.
Neve B, Fernandez-Zapico ME, Ashkenazi-Katalan V, Dina C, Hamid YH, Joly E, Vaillant E, Benmezroua Y, Durand E, Bakaher N, Delannoy V, Vaxillaire M, Cook T, Dallinga-Thie GM, Jansen H, Charles MA, Clément K, Galan P, Hercberg S, Helbecque N, Charpentier G, Prentki M, Hansen T, Pedersen O, Urrutia R, Melloul D, Froguel P. Role of transcription factor KLF11 and its diabetes-associated gene variants in pancreatic beta cell function. Proc Natl Acad Sci U S A. 2005;102(13):4807-12. doi:10.1073/pnas.0409177102. Epub 2005 Mar 17. PMID: 15774581.
Genetic testing for glucokinase mutations in clinically selected patients with MODY: a worthwhile investment. Schnyder S, et al. Swiss Med Wkly. 2005;135(23-24):352-6. doi:10.4414/smw.2005.11030. PMID: 16059790.
Raeder H, Johansson S, Holm PI, Haldorsen IS, Mas E, Sbarra V, Nermoen I, Eide SA, Grevle L, Bjørkhaug L, Sagen JV, Aksnes L, Søvik O, Lombardo D, Molven A, Njølstad PR. Mutations in the CEL VNTR cause a syndrome of diabetes and pancreatic exocrine dysfunction. Nat Genet. 2006;38(1):54-62. doi:10.1038/ng1708. Epub 2005 Dec 20. PMID: 16369531.
Plengvidhya N, Kooptiwut S, Songtawee N, Doi A, Furuta H, Nishi M, Nanjo K, Tantibhedhyangkul W, Boonyasrisawat W, Yenchitsomanus PT, Doria A, Banchuin N. PAX4 mutations in Thais with maturity onset diabetes of the young. J Clin Endocrinol Metab. 2007;92(7):2821-6. doi:10.1210/jc.2006-1927. Epub 2007 Apr 10. PMID: 17426099.
Edghill EL, Flanagan SE, Patch AM, Boustred C, Parrish A, Shields B, Shepherd MH, Hussain K, Kapoor RR, Malecki M, MacDonald MJ, Støy J, Steiner DF, Philipson LH, Bell GI, , Hattersley AT, Ellard S. Insulin mutation screening in 1,044 patients with diabetes: mutations in the INS gene are a common cause of neonatal diabetes but a rare cause of diabetes diagnosed in childhood or adulthood. Diabetes. 2008;57(4):1034-42. doi:10.2337/db07-1405. Epub 2007 Dec 27. PMID: 18162506.
Molven A, Ringdal M, Nordbø AM, Raeder H, Støy J, Lipkind GM, Steiner DF, Philipson LH, Bergmann I, Aarskog D, Undlien DE, Joner G, Søvik O, , Bell GI, Njølstad PR. Mutations in the insulin gene can cause MODY and autoantibody-negative type 1 diabetes. Diabetes. 2008;57(4):1131-5. doi:10.2337/db07-1467. Epub 2008 Jan 11. PMID: 18192540.
Ellard S, Bellanné-Chantelot C, Hattersley AT, . Best practice guidelines for the molecular genetic diagnosis of maturity-onset diabetes of the young. Diabetologia. 2008;51(4):546-53. doi:10.1007/s00125-008-0942-y. Epub 2008 Feb 23. PMID: 18297260.
Murphy R, Ellard S, Hattersley AT. Clinical implications of a molecular genetic classification of monogenic beta-cell diabetes. Nat Clin Pract Endocrinol Metab. 2008;4(4):200-13. doi:10.1038/ncpendmet0778. Epub 2008 Feb 26. PMID: 18301398.
Borowiec M, Liew CW, Thompson R, Boonyasrisawat W, Hu J, Mlynarski WM, El Khattabi I, Kim SH, Marselli L, Rich SS, Krolewski AS, Bonner-Weir S, Sharma A, Sale M, Mychaleckyj JC, Kulkarni RN, Doria A. Mutations at the BLK locus linked to maturity onset diabetes of the young and beta-cell dysfunction. Proc Natl Acad Sci U S A. 2009;106(34):14460-5. doi:10.1073/pnas.0906474106. Epub 2009 Aug 10. PMID: 19667185.
Rubio-Cabezas O, Minton JA, Kantor I, Williams D, Ellard S, Hattersley AT. Homozygous mutations in NEUROD1 are responsible for a novel syndrome of permanent neonatal diabetes and neurological abnormalities. Diabetes. 2010;59(9):2326-31. doi:10.2337/db10-0011. Epub 2010 Jun 23. PMID: 20573748.
Bowman P, Flanagan SE, Edghill EL, Damhuis A, Shepherd MH, Paisey R, Hattersley AT, Ellard S. Heterozygous ABCC8 mutations are a cause of MODY. Diabetologia. 2012;55(1):123-7. doi:10.1007/s00125-011-2319-x. Epub 2011 Oct 12. PMID: 21989597.
Johansson S, Irgens H, Chudasama KK, Molnes J, Aerts J, Roque FS, Jonassen I, Levy S, Lima K, Knappskog PM, Bell GI, Molven A, Njølstad PR. Exome sequencing and genetic testing for MODY. PLoS One. 2012;7(5):e38050. doi:10.1371/journal.pone.0038050. Epub 2012 May 25. PMID: 22662265.
Bonnefond A, Philippe J, Durand E, Dechaume A, Huyvaert M, Montagne L, Marre M, Balkau B, Fajardy I, Vambergue A, Vatin V, Delplanque J, Le Guilcher D, De Graeve F, Lecoeur C, Sand O, Vaxillaire M, Froguel P. Whole-exome sequencing and high throughput genotyping identified KCNJ11 as the thirteenth MODY gene. PLoS One. 2012;7(6):e37423. doi:10.1371/journal.pone.0037423. Epub 2012 Jun 11. PMID: 22701567.
McDonald TJ, Ellard S. Maturity onset diabetes of the young: identification and diagnosis. Ann Clin Biochem. 2013;50(Pt 5):403-15. doi:10.1177/0004563213483458. Epub 2013 Jul 22. PMID: 23878349.
Early-onset type-II diabetes mellitus (MODY4) linked to IPF1. Stoffers DA, et al. Nat Genet. 1997;17(2):138-9. doi:10.1038/ng1097-138. PMID: 9326926.

Clinical utility:

Establish or confirm diagnosis

View citations (16)

Mutations in NEUROD1 are associated with the development of type 2 diabetes mellitus. Malecki MT, et al. Nat Genet. 1999;23(3):323-8. doi:10.1038/15500. PMID: 10545951.
Neve B, Fernandez-Zapico ME, Ashkenazi-Katalan V, Dina C, Hamid YH, Joly E, Vaillant E, Benmezroua Y, Durand E, Bakaher N, Delannoy V, Vaxillaire M, Cook T, Dallinga-Thie GM, Jansen H, Charles MA, Clément K, Galan P, Hercberg S, Helbecque N, Charpentier G, Prentki M, Hansen T, Pedersen O, Urrutia R, Melloul D, Froguel P. Role of transcription factor KLF11 and its diabetes-associated gene variants in pancreatic beta cell function. Proc Natl Acad Sci U S A. 2005;102(13):4807-12. doi:10.1073/pnas.0409177102. Epub 2005 Mar 17. PMID: 15774581.
Genetic testing for glucokinase mutations in clinically selected patients with MODY: a worthwhile investment. Schnyder S, et al. Swiss Med Wkly. 2005;135(23-24):352-6. doi:10.4414/smw.2005.11030. PMID: 16059790.
Raeder H, Johansson S, Holm PI, Haldorsen IS, Mas E, Sbarra V, Nermoen I, Eide SA, Grevle L, Bjørkhaug L, Sagen JV, Aksnes L, Søvik O, Lombardo D, Molven A, Njølstad PR. Mutations in the CEL VNTR cause a syndrome of diabetes and pancreatic exocrine dysfunction. Nat Genet. 2006;38(1):54-62. doi:10.1038/ng1708. Epub 2005 Dec 20. PMID: 16369531.
Plengvidhya N, Kooptiwut S, Songtawee N, Doi A, Furuta H, Nishi M, Nanjo K, Tantibhedhyangkul W, Boonyasrisawat W, Yenchitsomanus PT, Doria A, Banchuin N. PAX4 mutations in Thais with maturity onset diabetes of the young. J Clin Endocrinol Metab. 2007;92(7):2821-6. doi:10.1210/jc.2006-1927. Epub 2007 Apr 10. PMID: 17426099.
Edghill EL, Flanagan SE, Patch AM, Boustred C, Parrish A, Shields B, Shepherd MH, Hussain K, Kapoor RR, Malecki M, MacDonald MJ, Støy J, Steiner DF, Philipson LH, Bell GI, , Hattersley AT, Ellard S. Insulin mutation screening in 1,044 patients with diabetes: mutations in the INS gene are a common cause of neonatal diabetes but a rare cause of diabetes diagnosed in childhood or adulthood. Diabetes. 2008;57(4):1034-42. doi:10.2337/db07-1405. Epub 2007 Dec 27. PMID: 18162506.
Molven A, Ringdal M, Nordbø AM, Raeder H, Støy J, Lipkind GM, Steiner DF, Philipson LH, Bergmann I, Aarskog D, Undlien DE, Joner G, Søvik O, , Bell GI, Njølstad PR. Mutations in the insulin gene can cause MODY and autoantibody-negative type 1 diabetes. Diabetes. 2008;57(4):1131-5. doi:10.2337/db07-1467. Epub 2008 Jan 11. PMID: 18192540.
Ellard S, Bellanné-Chantelot C, Hattersley AT, . Best practice guidelines for the molecular genetic diagnosis of maturity-onset diabetes of the young. Diabetologia. 2008;51(4):546-53. doi:10.1007/s00125-008-0942-y. Epub 2008 Feb 23. PMID: 18297260.
Murphy R, Ellard S, Hattersley AT. Clinical implications of a molecular genetic classification of monogenic beta-cell diabetes. Nat Clin Pract Endocrinol Metab. 2008;4(4):200-13. doi:10.1038/ncpendmet0778. Epub 2008 Feb 26. PMID: 18301398.
Borowiec M, Liew CW, Thompson R, Boonyasrisawat W, Hu J, Mlynarski WM, El Khattabi I, Kim SH, Marselli L, Rich SS, Krolewski AS, Bonner-Weir S, Sharma A, Sale M, Mychaleckyj JC, Kulkarni RN, Doria A. Mutations at the BLK locus linked to maturity onset diabetes of the young and beta-cell dysfunction. Proc Natl Acad Sci U S A. 2009;106(34):14460-5. doi:10.1073/pnas.0906474106. Epub 2009 Aug 10. PMID: 19667185.
Rubio-Cabezas O, Minton JA, Kantor I, Williams D, Ellard S, Hattersley AT. Homozygous mutations in NEUROD1 are responsible for a novel syndrome of permanent neonatal diabetes and neurological abnormalities. Diabetes. 2010;59(9):2326-31. doi:10.2337/db10-0011. Epub 2010 Jun 23. PMID: 20573748.
Bowman P, Flanagan SE, Edghill EL, Damhuis A, Shepherd MH, Paisey R, Hattersley AT, Ellard S. Heterozygous ABCC8 mutations are a cause of MODY. Diabetologia. 2012;55(1):123-7. doi:10.1007/s00125-011-2319-x. Epub 2011 Oct 12. PMID: 21989597.
Johansson S, Irgens H, Chudasama KK, Molnes J, Aerts J, Roque FS, Jonassen I, Levy S, Lima K, Knappskog PM, Bell GI, Molven A, Njølstad PR. Exome sequencing and genetic testing for MODY. PLoS One. 2012;7(5):e38050. doi:10.1371/journal.pone.0038050. Epub 2012 May 25. PMID: 22662265.
Bonnefond A, Philippe J, Durand E, Dechaume A, Huyvaert M, Montagne L, Marre M, Balkau B, Fajardy I, Vambergue A, Vatin V, Delplanque J, Le Guilcher D, De Graeve F, Lecoeur C, Sand O, Vaxillaire M, Froguel P. Whole-exome sequencing and high throughput genotyping identified KCNJ11 as the thirteenth MODY gene. PLoS One. 2012;7(6):e37423. doi:10.1371/journal.pone.0037423. Epub 2012 Jun 11. PMID: 22701567.
McDonald TJ, Ellard S. Maturity onset diabetes of the young: identification and diagnosis. Ann Clin Biochem. 2013;50(Pt 5):403-15. doi:10.1177/0004563213483458. Epub 2013 Jul 22. PMID: 23878349.
Early-onset type-II diabetes mellitus (MODY4) linked to IPF1. Stoffers DA, et al. Nat Genet. 1997;17(2):138-9. doi:10.1038/ng1097-138. PMID: 9326926.

Target population:

The target population for this test is patients suspected of having a diagnosis of MODY Tier 2.

Variant Interpretation:

What is the protocol for interpreting a variation as a VUS?
Variants are identified and evaluated using a custom collection of bioinformatic tools and comprehensively interpreted by our team of directors and genetic counselors.

Will the lab re-contact the ordering physician if variant interpretation changes?
Yes.

Research:

Is research allowed on the sample after clinical testing is complete?
http://dnatesting.uchicago.edu/research-consent-form

Recommended fields not provided:

Are family members with defined clinical status recruited to assess significance of VUS without charge?, Sample negative report, Sample positive report

Technical Information

Availability:

Tests performed
Entire test performed in-house

Analytical Validity:

Analytical Sensitivity 99-100% Accuracy 100% Precision 100%

Assay limitations:

This assay covers the coding and immediate flanking regions of the included genes. Variants in the promoter region and in other non-coding regions will not be detected. Variants that occur within regions of high homology and/or repetitiveness may not be detected due to issues with alignment. The technical sensitivity of … View more

Proficiency testing (PT):

Is proficiency testing performed for this test?
Yes

Method used for proficiency testing:
Formal PT program

PT Provider:
American College of Medical Genetics / College of American Pathologists, ACMG/CAP

VUS:

Software used to interpret novel variations
A custom collection of bioinformatics tools

Laboratory's policy on reporting novel variations
The laboratory reports novel variations.

Recommended fields not provided:

Test Confirmation, Citations to support assay limitations, Description of internal test validation method, Citations for Analytical validity, Description of PT method, Major CAP category, CAP category, CAP test list

Regulatory Approval

FDA Review:

Category: FDA exercises enforcement discretion

Additional Information

Reviews:

Genereviews

PubMed Clinical Queries

Clinical resources:

Molecular resources:

View GCK variations in ClinVar

RefSeqGene

Coriell Institute for Medical Research

Consumer resources:

MalaCards

MedlinePlusGenetics (GHR)

NCATS Office of Rare Diseases Research (GARD)

MedlinePlus

IMPORTANT NOTE: NIH does not independently verify information submitted to GTR; it relies on submitters to provide information that is accurate and not misleading. NIH makes no endorsements of tests or laboratories listed in GTR. GTR is not a substitute for medical advice. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.