X-linked Nance-Horan Syndrome and Congenital Cataract via the NHS Gene
Summary and Pricing 
Test Method
Exome Sequencing with CNV Detection
| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 11513 | NHS | 81479 | 81479,81479 | $990 | Order Options and Pricing |
Pricing Comments
Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).
Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).
The Sanger Sequencing method for this test is NY State approved.
For Sanger Sequencing click here.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
Nance-Horan syndrome (NHS) is a rare X-linked disorder which is characterized by severe congenital cataracts with microcornea, prominent dental findings, dysmorphic features, and mental retardation in some cases (Toutain et al. 1997; Stambolian et al. 1990). This disorder is reported to be inherited in codominant manner. Female carriers exhibit similar but less severe symptoms than affected males (van Dorp and Delleman 1979; Burdon et al. 2003). All affected males reported required cataract extraction in the first few months of life (Coccia et al. 2009).
Genetics
X-linked Nance-Horan syndrome is reported to be a homogeneous disorder, which is caused by mutations in NHS gene. NHS encodes three isoforms due to alternative splicing (isoform A, B and C). Isoform A, which is localized to the lens epithelium at the cellular periphery, is thought to be important in the pathogenesis of NHS (Sharma et al. 2008; Coccia et al. 2009). NHS protein is reported to be involved in the development of ocular, craniofacial, and neural tissue (Burdon et al. 2003). NHS mutations that lead to the NHS phenotype are all null mutations, which are predicted to produce no functional protein (Coccia et al. 2009). So far, about 35 NHS mutations (nonsense, splicing, regulatory, small and gross insertions and deletions and complex rearrangements) have been reported that are causative for NHS and X-linked congenital cataract (CXN)(Human Gene Mutation Database; Coccia et al. 2009).
Clinical Sensitivity - Sequencing with CNV PGxome
NHS mutation screening in seven NHS families revealed NHS protein truncating mutations in six of the families (Coccia et al. 2009). Another mutation analysis also detected NHS protein truncating mutations in six out of ten unrelated NHS patients from four different countries (Sharma et al. 2008). Another study detected NHS protein truncating mutations in all three NHS pedigrees (Brooks 2004).
NHS mutation screening in seven NHS affected families revealed a large deletion that encompasses a major portion of the NHS gene (exons 2-8) in one family. Also, two CXN families (negative for NHS sequencing) were reported to have a complex duplication–triplication re-arrangement and an intragenic deletion, which resulted in altered transcriptional regulation of the NHS gene (Coccia et al. 2009).
Testing Strategy
This test provides full coverage of all coding exons of the NHS gene 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 full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).
Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).
Indications for Test
All patients with symptoms suggestive of Nance-Horan syndrome (NHS) and X-linked congenital cataract are candidates.
All patients with symptoms suggestive of Nance-Horan syndrome (NHS) and X-linked congenital cataract are candidates.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| NHS | 300457 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Diseases
| Name | Inheritance | OMIM ID |
|---|---|---|
| Cataract, Congenital, X-Linked | XL | 302200 |
| Nance-Horan Syndrome | XL | 302350 |
Citations
- Brooks SP. 2004. Identification of the gene for Nance-Horan syndrome (NHS). Journal of Medical Genetics 41: 768–771. PubMed ID: 15466011
- Burdon KP, McKay JD, Sale MM, Russell-Eggitt IM, Mackey DA, Wirth MG, Elder JE, Nicoll A, Clarke MP, FitzGerald LM, others. 2003. Mutations in a Novel Gene, NHS, Cause the Pleiotropic Effects of Nance-Horan Syndrome, Including Severe Congenital Cataract, Dental Anomalies, and Mental Retardation. The American Journal of Human Genetics 73: 1120–1130. PubMed ID: 14564667
- Burdon KP, McKay JD, Sale MM, Russell-Eggitt IM, Mackey DA, Wirth MG, Elder JE, Nicoll A, Clarke MP, FitzGerald LM, Stankovich JM, Shaw MA, et al. 2003. Mutations in a Novel Gene, NHS, Cause the Pleiotropic Effects of Nance-Horan Syndrome, Including Severe Congenital Cataract, Dental Anomalies, and Mental Retardation. Am J Hum Genet 73: 1120–1130.
- Coccia M, Brooks SP, Webb TR, Christodoulou K, Wozniak IO, Murday V, Balicki M, Yee HA, Wangensteen T, Riise R, Saggar AK, Park S-M, et al. 2009. X-linked cataract and Nance-Horan syndrome are allelic disorders. Human Molecular Genetics 18: 2643–2655. PubMed ID: 19414485
- Human Gene Mutation Database (Bio-base).
- Sharma S, Burdon KP, Dave A, Jamieson RV, Yaron Y, Billson F, Maldergem L Van, Lorenz B, Gécz J, Craig JE. 2008. Novel causative mutations in patients with Nance-Horan syndrome and altered localization of the mutant NHS-A protein isoform. Molecular vision 14: 1856. PubMed ID: 18949062
- Stambolian D. et al. 1990. American journal of human genetics. 47: 13-9. PubMed ID: 1971992
- Toutain A. et al. 1997. Human genetics. 99: 256-61. PubMed ID: 9048931
- van Dorp DB, Delleman JW. 1979. A family with X-chromosomal recessive congenital cataract, microphthalmia, a peculiar form of the ear and dental anomalies. J Pediatr Ophthalmol Strabismus 16: 166–171. PubMed ID: 458526
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
If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.
Specimen Types
Specimen Requirements and Shipping Details
PGxome (Exome) Sequencing Panel
PGnome (Genome) Sequencing Panel
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ORDER OPTIONS
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2) Select Additional Test Options
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