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Wolfram syndrome panel
Clinical Genetic Test
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offered by
Genetic Services Laboratory
View lab's test page
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GTR Test Accession: Help GTR000506296.3
CAP
SYNDROMIC DISEASEINHERITED DISEASE
Last updated in GTR: 2020-08-13
View version history
Last annual review date for the lab: 2023-07-18 LinkOut
At a Glance
Test purpose: Help
Monitoring; Pre-symptomatic; Screening; ...
Conditions (2): Help
Wolfram syndrome; Wolfram syndrome 2
Genes (2): Help
CISD2 (4q24), WFS1 (4p16.1)
Methods (2): Help
Molecular Genetics - Deletion/duplication analysis: Next-Generation (NGS)/Massively parallel sequencing (MPS); ...
Target population: Help
The target population for this test is patients who are …
Clinical validity: Help
WFS1 encodes a glycoprotein called wolframin, which predominantly localizes to …
Clinical utility: Help
Establish or confirm diagnosis
Ordering Information
Offered by: Help
Genetic Services Laboratory
View lab's website
View lab's test page
Specimen Source: Help
Who can order: Help
  • Genetic Counselor
  • Registered Nurse
  • Health Care Provider
  • Licensed Physician
  • Nurse Practitioner
  • Physician Assistant
CPT codes: Help
**AMA CPT codes notice

Copyright: 2023 American Medical Association. All rights reserved.

Contact Policy: Help
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: Help
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: Help
Clinical Testing/Confirmation of Mutations Identified Previously
Confirmation of research findings
Test additional service: Help
Custom Prenatal Testing
Custom mutation-specific/Carrier testing
Test development: Help
Test developed by laboratory (no manufacturer test name)
Informed consent required: Help
No
Pre-test genetic counseling required: Help
Decline to answer
Post-test genetic counseling required: Help
Decline to answer
Recommended fields not provided:
Test Order Code, Lab contact for this test, Test strategy
Conditions Help
Total conditions: 2
Condition/Phenotype Identifier
Test Targets
Genes Help
Total genes: 2
Gene Associated Condition Germline or Somatic Allele (Lab-provided) Variant in NCBI
Methodology
Total methods: 2
Method Category Help
Test method Help
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: Help
Monitoring; Pre-symptomatic; Screening; Mutation Confirmation; Diagnosis; Risk Assessment
Clinical validity: Help
WFS1 encodes a glycoprotein called wolframin, which predominantly localizes to the endoplasmic reticulum. Mutations associated with Wolfram syndrome typically lead to a loss of protein function, whereas non-activating mutations have been identified in heterozygous carriers with autosomal dominant low frequency sensorineural hearing loss. CISD2 encodes an intermembrane protein in the … View more
View citations (3)
  • Mutational spectrum of the WFS1 gene in Wolfram syndrome, nonsyndromic hearing impairment, diabetes mellitus, and psychiatric disease. Cryns K, et al. Hum Mutat. 2003;22(4):275-87. doi:10.1002/humu.10258. PMID: 12955714.
  • Amr S, Heisey C, Zhang M, Xia XJ, Shows KH, Ajlouni K, Pandya A, Satin LS, El-Shanti H, Shiang R. A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2. Am J Hum Genet. 2007;81(4):673-83. doi:10.1086/520961. Epub 2007 Aug 20. PMID: 17846994.
  • Rendtorff ND, Lodahl M, Boulahbel H, Johansen IR, Pandya A, Welch KO, Norris VW, Arnos KS, Bitner-Glindzicz M, Emery SB, Mets MB, Fagerheim T, Eriksson K, Hansen L, Bruhn H, Möller C, Lindholm S, Ensgaard S, Lesperance MM, Tranebjaerg L. Identification of p.A684V missense mutation in the WFS1 gene as a frequent cause of autosomal dominant optic atrophy and hearing impairment. Am J Med Genet A. 2011;155A(6):1298-313. doi:10.1002/ajmg.a.33970. Epub 2011 Apr 28. PMID: 21538838.
Clinical utility: Help
Establish or confirm diagnosis
View citations (3)
  • Mutational spectrum of the WFS1 gene in Wolfram syndrome, nonsyndromic hearing impairment, diabetes mellitus, and psychiatric disease. Cryns K, et al. Hum Mutat. 2003;22(4):275-87. doi:10.1002/humu.10258. PMID: 12955714.
  • Amr S, Heisey C, Zhang M, Xia XJ, Shows KH, Ajlouni K, Pandya A, Satin LS, El-Shanti H, Shiang R. A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2. Am J Hum Genet. 2007;81(4):673-83. doi:10.1086/520961. Epub 2007 Aug 20. PMID: 17846994.
  • Rendtorff ND, Lodahl M, Boulahbel H, Johansen IR, Pandya A, Welch KO, Norris VW, Arnos KS, Bitner-Glindzicz M, Emery SB, Mets MB, Fagerheim T, Eriksson K, Hansen L, Bruhn H, Möller C, Lindholm S, Ensgaard S, Lesperance MM, Tranebjaerg L. Identification of p.A684V missense mutation in the WFS1 gene as a frequent cause of autosomal dominant optic atrophy and hearing impairment. Am J Med Genet A. 2011;155A(6):1298-313. doi:10.1002/ajmg.a.33970. Epub 2011 Apr 28. PMID: 21538838.

Target population: Help
The target population for this test is patients who are suspected of having a diagnosis of Wolfram syndrome.
Variant Interpretation:
What is the protocol for interpreting a variation as a VUS? Help
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? Help
Yes.
Research:
Is research allowed on the sample after clinical testing is complete? Help
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: Help
Tests performed
Entire test performed in-house
Analytical Validity: Help
Analytical Sensitivity 99-100% Accuracy 100% Precision 100%
Assay limitations: Help
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? Help
Yes

Method used for proficiency testing: Help
Formal PT program

PT Provider: Help
American College of Medical Genetics / College of American Pathologists, ACMG/CAP
VUS:
Software used to interpret novel variations Help
A custom collection of bioinformatics tools

Laboratory's policy on reporting novel variations Help
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: Help
Category: FDA exercises enforcement discretion
Additional Information

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.