GTR Home > Tests > Neonatal Diabetes Mellitus Deletion/Duplication Analysis

Overview

Test name

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Neonatal Diabetes Mellitus Deletion/Duplication Analysis

Purpose of the test

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This is a clinical test intended for Help: Diagnosis, Monitoring, Mutation Confirmation, Pre-symptomatic, Risk Assessment, Screening

Condition

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1 condition tested. Click Indication tab for more information.

Methodology

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Molecular Genetics
DDeletion/duplication analysis
Microarray

Summary of what is tested

8 genes and variants. Click Methodology tab for more information.

Genes

Clinical validity

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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).

Citations
  • X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. - PubMed ID: 11137992
  • Hypomethylation of multiple imprinted loci in individuals with transient neonatal diabetes is associated with mutations in ZFP57. - PubMed ID: 18622393
  • Wolcott-Rallison syndrome is the most common genetic cause of permanent neonatal diabetes in consanguineous families. - PubMed ID: 19837917
  • De León DD, Stanley CA. Permanent Neonatal Diabetes Mellitus. 2008 Feb 8 [Updated 2011 Jul 5]. In: Pagon RA, Adam MP, Bird TD, et al., editors. GeneReviews™ [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2013. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1447/

Clinical utility

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Establish or confirm diagnosis

Citations
  • X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. - PubMed ID: 11137992
  • Hypomethylation of multiple imprinted loci in individuals with transient neonatal diabetes is associated with mutations in ZFP57. - PubMed ID: 18622393
  • Wolcott-Rallison syndrome is the most common genetic cause of permanent neonatal diabetes in consanguineous families. - PubMed ID: 19837917

How to order

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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 Help: http://dnatesting.uchicago.edu/submitting-sample

Test services

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  • Clinical Testing/Confirmation of Mutations Identified Previously
  • Confirmation of research findings
  • Custom Prenatal Testing
  • Custom mutation-specific/Carrier testing

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