Johanson-Blizzard Syndrome via the UBR1 Gene
Summary and Pricing 
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 3033 | UBR1 | 81479 | 81479,81479 | $640 | 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.
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
Johanson-Blizzard syndrome (JBS) is a rare congenital multisystem malformation syndrome characterized by nasal wing hypoplasia and exocrine pancreatic insufficiency. Additional common clinical features of JBS include hypothyroidism, sensorineural hearing loss, short stature, scalp defects, dental abnormalities, genitourinary malformations, and intellectual disability. The prevalence of JBS is estimated to be about 1 in 250,000 live births in Europe. More than 60 patients have been reported to date (Sukalo et al. 2014; Hwang et al. 2011; Zenker et al. 2005).
Genetics
Johanson-Blizzard syndrome (JBS) is an autosomal recessive disorder due to loss of function pathogenic variants in the UBR1 gene. UBR1 encodes one of the E3 ubiquitin ligases of the N-end rule pathway. Documented UBR1 mutation types include missense, nonsense, splicing variants, and small deletions/insertions. Missense variants and in-frame deletions are reported to be associated with milder clinical manifestations. No gross deletions/duplications affecting the UBR1 gene have been reported so far (Sukalo et al. 2014; Hwang et al. 2011; Zenker et al. 2005).
Clinical Sensitivity - Sequencing with CNV PG-Select
UBR1 pathogenic variants are the only known cause of Johanson-Blizzard syndrome (JBS). The reported mutation detection rate is ~97% in patients with a clinically well-defined JBS phenotype. No gross deletion and duplication variants affecting the UBR1 gene have been reported so far (Sukalo et al. 2014).
Testing Strategy
This test provides full coverage of all coding exons of the UBR1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.
Indications for Test
Individuals with clinical symptoms consistent with nasal wing hypoplasia and exocrine pancreatic insufficiency. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in UBR1.
Individuals with clinical symptoms consistent with nasal wing hypoplasia and exocrine pancreatic insufficiency. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in UBR1.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| UBR1 | 605981 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Johanson-Blizzard Syndrome | AR | 243800 |
Related Test
| Name |
|---|
| Congenital Hypothyroidism and Thyroid Hormone Resistance Panel |
Citations
- Hwang C-S, Sukalo M, Batygin O, Addor M-C, Brunner H, Aytes AP, Mayerle J, Song HK, Varshavsky A, Zenker M. 2011. Ubiquitin ligases of the N-end rule pathway: assessment of mutations in UBR1 that cause the Johanson-Blizzard syndrome. PLoS ONE 6: e24925. PubMed ID: 21931868
- Sukalo M, Fiedler A, Guzmán C, Spranger S, Addor M-C, McHeik JN, Oltra Benavent M, Cobben JM, Gillis LA, Shealy AG, Deshpande C, Bozorgmehr B, Everman DB, Stattin EL, Liebelt J, Keller KM, Bertola DR, van Karnebeek CD, Bergmann C, Liu Z, Düker G, Rezaei N, Alkuraya FS, Ogur G, Alrajoudi A, Venegas-Vega CA, Verbeek NE, Richmond EJ, Kirbiyik O, Ranganath P, Singh A, Godbole K, Ali FA, Alves C, Mayerle J, Lerch MM, Witt H, Zenker M. 2014. Mutations in the human UBR1 gene and the associated phenotypic spectrum. Hum. Mutat. 35: 521–531. PubMed ID: 24599544
- Zenker M, Mayerle J, Lerch MM, Tagariello A, Zerres K, Durie PR, Beier M, Hülskamp G, Guzman C, Rehder H, Beemer FA, Hamel B, Vanlieferinghen P, Gershoni-Baruch R, Vieira MW, Dumic M, Auslender R, Gil-da-Silva-Lopes VL, Steinlicht S, Rauh M, Shalev SA, Thiel C, Ekici AB, Winterpacht A, Kwon YT, Varshavsky A, Reis A. 2005. Deficiency of UBR1, a ubiquitin ligase of the N-end rule pathway, causes pancreatic dysfunction, malformations and mental retardation (Johanson-Blizzard syndrome). Nat. Genet. 37: 1345–1350. PubMed ID: 16311597
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
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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.