Waardenburg Syndrome Type IIA via the MITF Gene
Summary and Pricing 
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture ProbesTest Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
---|---|---|---|---|---|
8401 | MITF | 81479 | 81479,81479 | $990 | Order Options and Pricing |
Pricing Comments
This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
Testing run on PG-Select capture probes does not include exome-wide CNV analysis. Reflex is available to PGxome or an exome-based panel, or you can use this gene list to create a custom panel (click here).
Click here for costs to reflex to whole PGxome.
Turnaround Time
3 weeks on average for standard orders or 2 weeks on average for STAT orders.
Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.
Targeted Testing
For ordering sequencing of targeted known variants, go to our Targeted Variants page.
Clinical Features and Genetics 
Clinical Features
Waardenburg syndrome (WS) is an auditory-pigmentary disorder characterized by congenital sensorineural hearing loss and pigmentary abnormalities of the hair, including a white forelock, and pigmentary changes of the iris such as heterochromia. WS is classified into 4 main types depending on the clinical symptoms and has causative mutations in different genes (Pingault et al., 2010).
WS I : Auditory-pigmentary abnormalities along with dystopia canthorum (lateral displacement of the inner canthi), caused by mutations in PAX3.
WS II : Auditory-pigmentary abnormalities without dystopia canthorum, caused by mutations in MITF, SNAI2, and SOX10.
WS III : Type I with musculo-skeletal abnormalities of the upper limb (Klein-Waardenburg syndrome), caused by mutations in PAX3.
WS IV : Type II with Hirschsprung disease (Waardenburg-Shah syndrome), caused by mutations in EDN3, EDNRB, and SOX10.
WS type II is typified by sensorineural hearing loss and heterochromia iridumis observed in approximately 77% and 47% of affected individuals respectively, and is much more common than WS type I (Liu et al., 1995). Dystopia canthorum is NOT observed in WS II. Other clinical manifestations such as the classic white forelock are more common in WS1.
Genetics
WS type II is an autosomal dominant syndrome caused by heterozygous mutations in the MITF gene. MITF, the microphthalmia-associated transcription factor, helps control the development and function of pigment-producing cells called melanocytes, which produce the pigment melanin, contributing to hair, eye, and skin color. Melanocytes are also found in the inner ear and play an important role in hearing. Mutations in MITF alter protein dimerization impacting melanocyte development (Widlund and Fisher, 2003). Shortage of melanocytes results in hypopigmentation and hearing loss characteristic of Waardenburg syndrome. It is estimated that MITF mutations are observed in 15% of individuals with WS2 (Read and Newton, 1997). Mutations include missense, truncating, splicing alterations along with deletions and insertions. Digenic inheritance of WS with ocular albinism has been suggested (Chiang et al., 2009). Mutations in MITF are also known to be causative for Tietz syndrome (Smith et al., 2000).
Clinical Sensitivity - Sequencing with CNV PG-Select
It is estimated that MITF mutations are observed in 15% of individuals with WS2 (Read and Newton, 1997). Molecular genetic testing by sequencing of MITF detects more than 90% of disease-causing mutations.
Testing Strategy
This test provides full coverage of all coding exons of the MITF gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.
Indications for Test
Diagnostic criteria for Waardenburg syndrome type II (WSII) were outlined (Liu et al. 1995) and include three important indicators: Congenital sensorineural hearing loss, Complete heterochromia iridum (irides of different color), and Absence of Dystopia canthorum.
Diagnostic criteria for Waardenburg syndrome type II (WSII) were outlined (Liu et al. 1995) and include three important indicators: Congenital sensorineural hearing loss, Complete heterochromia iridum (irides of different color), and Absence of Dystopia canthorum.
Gene
Official Gene Symbol | OMIM ID |
---|---|
MITF | 156845 |
Inheritance | Abbreviation |
---|---|
Autosomal Dominant | AD |
Autosomal Recessive | AR |
X-Linked | XL |
Mitochondrial | MT |
Diseases
Name | Inheritance | OMIM ID |
---|---|---|
Albinism, Ocular, With Sensorineural Deafness | AD | 103470 |
Melanoma, cutaneous malignant, susceptibility to, 8 | AR | 614456 |
Tietz Syndrome | AD | 103500 |
Waardenburg Syndrome, Type 2A | AD | 193510 |
Related Tests
Name |
---|
Melanoma Panel |
Renal Cancer Panel |
Waardenburg Syndrome Panel |
Citations 
- Chiang P-W, Spector E, McGregor TL. 2009. Evidence suggesting digenic inheritance of Waardenburg syndrome type II with ocular albinism. Am. J. Med. Genet. A 149A: 2739–2744. PubMed ID: 19938076
- Liu XZ, Newton VE, Read AP. 1995. Waardenburg syndrome type II: phenotypic findings and diagnostic criteria. Am. J. Med. Genet. 55: 95–100. PubMed ID: 7702105
- Pingault V, Ente D, Dastot-Le Moal F, Goossens M, Marlin S, Bondurand N. 2010. Review and update of mutations causing Waardenburg syndrome. Human Mutation 31: 391–406. PubMed ID: 20127975
- Read AP, Newton VE. 1997. Waardenburg syndrome. Journal of medical genetics 34: 656–665. PubMed ID: 9279758
- Smith SD, Kelley PM, Kenyon JB, Hoover D. 2000. Tietz syndrome (hypopigmentation/deafness) caused by mutation ofMITF. Journal of medical genetics 37: 446–448. PubMed ID: 10851256
- Widlund HR, Fisher DE. 2003. Microphthalamia-associated transcription factor: a critical regulator of pigment cell development and survival. Oncogene 22: 3035–3041. PubMed ID: 12789278
Ordering/Specimens 
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.
- PGnome sequencing panels can be ordered via the myPrevent portal only at this time.
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
ORDER OPTIONS
View Ordering Instructions1) Select Test Type
2) Select Additional Test Options
STAT and Prenatal Test Options are not available with Patient Plus.
No Additional Test Options are available for this test.