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 GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
11513 NHS 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11513NHS81479 81479 $890 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.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Targeted Testing

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

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

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.

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

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.

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

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