Wolfram Syndrome Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10057 CISD2 81479,81479 Order Options and Pricing
WFS1 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10057Genes x (2)81479 81479 $890 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


Clinical Features and Genetics

Clinical Features

Wolfram syndrome (WFS) is a progressive neurodegenerative disorder characterized by onset of diabetes mellitus and optic atrophy before age 15 years, typically associated with sensorineural hearing loss, progressive neurologic abnormalities (ataxia, peripheral neuropathy, dementia, psychiatric illness, and urinary tract atony), and other endocrine abnormalities. Median age at death is 30 years. WFS1 is also sometimes referred to as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). Wolfram Syndrome Type 2 is characterized by juvenile-onset diabetes mellitus, optic atrophy, high-frequency sensorineural hearing impairment, urinary tract dilatation, impaired renal function, hypogonadism, and severe gastrointestinal ulcer and bleeding, but not diabetes insipidus (Amr et al. 2007; Tranebjaerg et al. 2009). WFS1-related disorders range from Wolfram syndrome (WFS1) to WFS1-related low-frequency sensory hearing loss (also known as DFNA6/14/38 low-frequency sensorineural hearing loss [LFSNHL]). WFS-like disorder is characterized by sensorineural hearing loss, diabetes mellitus, psychiatric illness, and variable optic atrophy. WFS1-related LFSNHL is characterized by congenital, nonsyndromic, slowly progressive, low-frequency (< 2000 Hz) sensorineural hearing loss (Tranebjaerg et al. 2009).


WFS1: Estimated prevalence is 1 in 500,000 people worldwide with an autosomal recessive mode of inheritance. Mutations in the WFS1 gene account for more than 90 percent of Wolfram syndrome type 1 cases. WFS1 produces a protein called wolframin that is thought to regulate the amount of calcium in cells. Mutations in the gene lead to reduced or absent function, causing disease. At least 200 variants in WFS1 have been found to cause Wolfram syndrome, including nonsense, missense, inframe deletions, duplications as well as frameshift mutations. WFS1-related Disorders: Though WFS1 is inherited in an autosomal recessive manner, carriers of WFS1 mutations do appear to have an increased risk of hearing impairment (Pennings et al. 2004), but it is as yet unknown whether they could be at higher risk for diabetes mellitus and psychiatric disorders (Swift et al. 1998). WFS-like disorder is inherited in an autosomal dominant manner. WFS2: Prevalence of CISD2-associated Wolfram syndrome type 2 is currently unknown. The exact function of the CISD2 protein is unknown, but limited studies suggest that it helps regulate mitochondrial function. Identification of a single homozygous missense mutation in affected individuals suggests an autosomal recessive mode of inheritance (El-Shanti et al. 2000). No other mutations have been identified.

Clinical Sensitivity - Sequencing with CNV PGxome

WFS1-related disorders occur due to a wide variety of mutations in the WFS1 gene, including nonsense, missense, inframe deletions and duplications as well as frameshift mutations. Most mutations occur in exon 8, and no founder mutations have thus far been identified (Hardy et al. 1999). Our full gene sequencing test is expected to detect >90% of WFS1 causative mutations (Khanim et al. 2001). Only a single homozygous missense mutation at c.109G>C (Glu37Gln) in CISD2 is known to be causative for WFS2 disease (El-Shanti et al. 2000). No other causative mutations have been identified.

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel provides full coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

The following are criteria sensitive and specific for WFS (Barrett et al. 1995): juvenile-onset (before age 15 years) diabetes mellitus, juvenile-onset optic atrophy, sensorineural hearing impairment (which can sometimes be congenital and severe), ataxia, dementia/ intellectual disability (both may occur, but intellectual disability is rare), psychiatric disease, and autosomal recessive inheritance. For WFS2, clinical manifestations do not include diabetes insipidus. For Wolfram syndrome-like disease, individuals presenting with LFSNHL, diabetes mellitus, psychiatric illness, optic atrophy (variable) and autosomal dominant inheritance.


Official Gene Symbol OMIM ID
CISD2 611507
WFS1 606201
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test



  • Amr S, Heisey C, Zhang M, Xia X-J, Shows KH, Ajlouni K, Pandya A, Satin LS, El-Shanti H, Shiang R. 2007. A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2. Am. J. Hum. Genet. 81: 673–683. PubMed ID: 17846994
  • Barrett TG, Poulton K, Bundey S. 1995. DIDMOAD syndrome; further studies and muscle biochemistry. J. Inherit. Metab. Dis. 18: 218–220. PubMed ID: 7564251
  • El-Shanti H, Lidral AC, Jarrah N, Druhan L, Ajlouni K. 2000. Homozygosity mapping identifies an additional locus for Wolfram syndrome on chromosome 4q. Am. J. Hum. Genet. 66: 1229–1236. PubMed ID: 10739754
  • Hardy C, Khanim F, Torres R, Scott-Brown M, Seller A, Poulton J, Collier D, Kirk J, Polymeropoulos M, Latif F, Barrett T. 1999. Clinical and molecular genetic analysis of 19 Wolfram syndrome kindreds demonstrating a wide spectrum of mutations in WFS1. Am. J. Hum. Genet. 65: 1279–1290. PubMed ID: 10521293
  • Khanim F, Kirk J, Latif F, Barrett TG. 2001. WFS1/wolframin mutations, Wolfram syndrome, and associated diseases. Hum. Mutat. 17: 357–367. PubMed ID: 11317350
  • Pennings RJE, Huygen PLM, Ouweland JMW van den, Cryns K, Dikkeschei LD, Camp G Van, Cremers CWRJ. 2004. Sex-related hearing impairment in Wolfram syndrome patients identified by inactivating WFS1 mutations. Audiol. Neurootol. 9: 51–62. PubMed ID: 14676474
  • Swift RG, Polymeropoulos MH, Torres R, Swift M. 1998. Predisposition of Wolfram syndrome heterozygotes to psychiatric illness. Mol. Psychiatry 3: 86–91. PubMed ID: 9491819
  • Tranebjaerg L, Barrett T, Rendtorff ND. 2009. WFS1-Related Disorders. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301750


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

Specimen Types

Specimen Requirements and Shipping Details

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View Ordering Instructions

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2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

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