Neonatal Diabetes Panel - Clinical Genetic Test - GTR

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Neonatal Diabetes Panel

Clinical Genetic Test

offered by

Genetic Services Laboratory

View lab's test page

GTR Test Accession: GTR000506427.6

CAP

INHERITED DISEASEIMMUNOLOGYCANCER ... 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 (3):

Neonatal diabetes mellitus; Combined immunodeficiency due to LRBA deficiency; STAT3-related early-onset multisystem autoimmune disease

Chromosomal regions/ Mitochondria (3):

MT-TE m.14709T>C; MT-TK m.8296A>G; MT-TL1 m.3243A>G

Genes (14):

ABCC8 (11p15.1); EIF2AK3 (2p11.2); FOXP3 (Xp11.23); GATA4 (8p23.1); GATA6 (18q11.2) 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:

The mode of inheritance of PNDM is autosomal dominant for …

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: 3

Condition/Phenotype	Identifier

Test Targets

Chromosomal regions/Mitochondria

Total chromosomal regions/mitochondria: 3

Chromosomal region/Mitochondrion	Associated condition

Genes

Total genes: 14

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:

The mode of inheritance of PNDM is autosomal dominant for mutations in KCNJ11, autosomal dominant or autosomal recessive for mutations in ABCC8 and INS, and autosomal recessive for mutations in GCK and PDX1. Individuals with autosomal dominant PNDM may have an affected parent or may have a de novo mutation. … The mode of inheritance of PNDM is autosomal dominant for mutations in KCNJ11, autosomal dominant or autosomal recessive for mutations in ABCC8 and INS, and autosomal recessive for mutations in GCK and PDX1. Individuals with autosomal dominant PNDM may have an affected parent or may have a de novo mutation. Each child of an individual with PNDM inherited in an autosomal dominant manner has a 50% chance of inheriting the mutation. The parents of a child with autosomal recessive PNDM are obligate heterozygotes and therefore carry one mutant allele. Heterozygotes (carriers) for mutations in GCK and PDX1 have a mild form of diabetes mellitus known as GCK-familial monogenic diabetes (formerly known as MODY2) and PDX1-familial monogenic diabetes (formerly known as MODY4). At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier (or of having familial monogenic diabetes), and a 25% chance of being unaffected and not a carrier. Prenatal diagnosis for pregnancies at increased risk is possible if the disease-causing mutation(s) in the family are known. Homozygous EIF2AK3 mutations cause Wolcott-Rallison syndrome (WRS; OMIM#226980) characterized by permanent neonatal or early infancy insulin-dependent diabetes. Other findings, including epiphyseal dysplasia, osteoporosis, and growth retardation develop at a later age. Other frequent multisystem manifestations include hepatic and renal dysfunction, intellectual disability, and cardiovascular abnormalities. Homozygous ZFP57 mutations are a rare cause of transient neonatal diabetes. Mutations in the X-linked gene FOXP3 cause IPEX (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked) syndrome, which is characterized by systemic autoimmunity, typically beginning in the first year of life. Presentation is most commonly the clinical triad of watery diarrhea, eczematous dermatitis, and endocrinopathy (most commonly insulin-dependent diabetes mellitus). View more

View citations (5)

X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Wildin RS, et al. Nat Genet. 2001;27(1):18-20. doi:10.1038/83707. PMID: 11137992.
Mackay DJ, Callaway JL, Marks SM, White HE, Acerini CL, Boonen SE, Dayanikli P, Firth HV, Goodship JA, Haemers AP, Hahnemann JM, Kordonouri O, Masoud AF, Oestergaard E, Storr J, Ellard S, Hattersley AT, Robinson DO, Temple IK. Hypomethylation of multiple imprinted loci in individuals with transient neonatal diabetes is associated with mutations in ZFP57. Nat Genet. 2008;40(8):949-51. doi:10.1038/ng.187. Epub 2008 Jul 11. PMID: 18622393.
Rubio-Cabezas O, Patch AM, Minton JA, Flanagan SE, Edghill EL, Hussain K, Balafrej A, Deeb A, Buchanan CR, Jefferson IG, Mutair A, , Hattersley AT, Ellard S. Wolcott-Rallison syndrome is the most common genetic cause of permanent neonatal diabetes in consanguineous families. J Clin Endocrinol Metab. 2009;94(11):4162-70. doi:10.1210/jc.2009-1137. Epub 2009 Oct 16. PMID: 19837917.
De León DD, Stanley CA. Permanent Neonatal Diabetes Mellitus. 2008 Feb 08 [updated 2016 Jul 29]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. PMID: 20301620.
https://www.ncbi.nlm.nih.gov/books/NBK1447

Clinical utility:

Establish or confirm diagnosis

View citations (5)

X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Wildin RS, et al. Nat Genet. 2001;27(1):18-20. doi:10.1038/83707. PMID: 11137992.
Mackay DJ, Callaway JL, Marks SM, White HE, Acerini CL, Boonen SE, Dayanikli P, Firth HV, Goodship JA, Haemers AP, Hahnemann JM, Kordonouri O, Masoud AF, Oestergaard E, Storr J, Ellard S, Hattersley AT, Robinson DO, Temple IK. Hypomethylation of multiple imprinted loci in individuals with transient neonatal diabetes is associated with mutations in ZFP57. Nat Genet. 2008;40(8):949-51. doi:10.1038/ng.187. Epub 2008 Jul 11. PMID: 18622393.
Rubio-Cabezas O, Patch AM, Minton JA, Flanagan SE, Edghill EL, Hussain K, Balafrej A, Deeb A, Buchanan CR, Jefferson IG, Mutair A, , Hattersley AT, Ellard S. Wolcott-Rallison syndrome is the most common genetic cause of permanent neonatal diabetes in consanguineous families. J Clin Endocrinol Metab. 2009;94(11):4162-70. doi:10.1210/jc.2009-1137. Epub 2009 Oct 16. PMID: 19837917.
De León DD, Stanley CA. Permanent Neonatal Diabetes Mellitus. 2008 Feb 08 [updated 2016 Jul 29]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. PMID: 20301620.
https://www.ncbi.nlm.nih.gov/books/NBK1447

Target population:

The target population for this test is patients suspected of having a diagnosis of Neonatal Diabetes Mellitus.

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:

PubMed Clinical Queries

Clinical resources:

Consumer resources:

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.