FRMD7-Associated X-linked Congenital Nystagmus 1 (NYS1) via the FRMD7 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 | |
|---|---|---|---|---|---|
| 9891 | FRMD7 | 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
Congenital nystagmus (CN) is a relatively common neurological-ocular disorder with an estimated prevalence of approximately 1/1000 live births. However, it can also occur early in the child’s vision development. CN is clinically characterized by bilateral involuntary rhythmic horizontal (predominant) and conjugate ocular oscillations that may result in significantly reduced visual acuity (Cabot et al. 1999; Tarpey et al. 2006; Sarvananthan et al. 2009; Zhu et al. 2013; Zhang et al. 2014).
Genetics
CN is a genetically heterogeneous disorder that is reported to exhibit X-linked, autosomal dominant and autosomal recessive modes of inheritance. To date, five chromosomal loci (NYS 1–5) have been mapped that are linked to CN pathogenesis (Thomas et al. 2011). FRMD7-associated CN is inherited in an X-linked mode with incomplete penetrance in female carriers (~50%) (Tarpey et al. 2006). FRMD7, which is located on Xq26-q27 encodes FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain-containing 7 protein, a member of FERM protein family. It has been reported that FRMD7 expression is spatiotemporally regulated in the brain during embryonic and fetal development, particularly in regions of the brain associated with oculomotor control. These results suggest that FRMD7 has a specific role in the control of eye movement and gaze stability (Betts-Henderson et al. 2010; Tarpey et al. 2006). Recently, Watkins et al. (2013) reports that FRMD7 mutations disrupt the FRMD7 interaction with CASK, a MAGUK (Membrane-associated guanylate kinases) family member, which further prevents their co-localization at the plasma membrane and impairs CASK-induced neurite outgrowth during development of the oculomotor neural network and results in nystagmus (Watkins et al. 2013). So far, about 50 pathogenic sequence variations (missense/nonsense, splicing, small insertions, small and gross deletions) in FRMD7 that are associated with X-linked Congenital Nystagmus 1 have been reported (Human Gene Mutation Database).
Clinical Sensitivity - Sequencing with CNV PGxome
A FRMD7 mutational screening in 14 families with two or more affected individuals of either sex identified mutations in 8 families (57%)(Tarpey et al. 2006). Also in the same study, in a cohort of 42 simplex cases (who had undergone careful clinical and electrophysiological investigation to exclude other causes of inherited CN, 3 patients (7%) were found to have FRMD7 mutations. All identified mutations were absent in 300 male control chromosomes. Another study showed that FRMD7 mutations account for approximately 47% of X-linked nystagmus in Chinese patients (Du et al. 2011). Analytical sensitivity is expected to be high because approximately 90% of the FRMD7 causative mutations are detectable by this method (Thomas et al. 1993). Only one large intragenic deletion in FRMD7 has been reported so far (Fingert et al. 2010).
Testing Strategy
This test provides full coverage of all coding exons of the FRMD7 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 nystagmus, even the simplex cases (please see the clinical sensitivity section).
All patients with symptoms suggestive of nystagmus, even the simplex cases (please see the clinical sensitivity section).
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| FRMD7 | 300628 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| X-Linked Infantile Nystagmus | XL | 310700 |
Citations
- Betts-Henderson J, Bartesaghi S, Crosier M, Lindsay S, Chen H-L, Salomoni P, Gottlob I, Nicotera P. 2010. The nystagmus-associated FRMD7 gene regulates neuronal outgrowth and development. Human Molecular Genetics 19: 342–351. PubMed ID: 19892780
- Cabot A, Rozet J-M, Gerber S, Perrault I, Ducroq D, Smahi A, Souied E, Munnich A, Kaplan J. 1999. A gene for X-linked idiopathic congenital nystagmus (NYS1) maps to chromosome Xp11. 4-p11. 3. The American Journal of Human Genetics 64: 1141–1146. PubMed ID: 10090899
- Du W, Bu J, Dong J, Jia Y, Li J, Liang C, Si S, Wang L. 2011. A novel frame-shift mutation in FRMD7 causes X-linked idiopathic congenital nystagmus in a Chinese family. Molecular vision 17: 2765. PubMed ID: 22065930
- Fingert JH, Roos B, Eyestone ME, Pham JD, Mellot ML, Stone E. 2010. Novel intragenic FRMD7 deletion in a pedigree with congenital X-linked nystagmus. Ophthalmic Genet. 31: 77–80. PubMed ID: 20450309
- Human Gene Mutation Database (Bio-base).
- Sarvananthan N, Surendran M, Roberts EO, Jain S, Thomas S, Shah N, Proudlock FA, Thompson JR, McLean RJ, Degg C, Woodruff G, Gottlob I. 2009. The Prevalence of Nystagmus: The Leicestershire Nystagmus Survey. Investigative Ophthalmology & Visual Science 50: 5201–5206. PubMed ID: 19458336
- Tarpey P, Thomas S, Sarvananthan N, Mallya U, Lisgo S, Talbot CJ, Roberts EO, Awan M, Surendran M, McLean RJ, Reinecke RD, Langmann A, et al. 2006. Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus. Nature Genetics 38: 1242–1244. PubMed ID: 17013395
- Thomas MG, Crosier M, Lindsay S, Kumar A, Thomas S, Araki M, Talbot CJ, McLean RJ, Surendran M, Taylor K, Leroy BP, Moore AT, et al. 2011. The clinical and molecular genetic features of idiopathic infantile periodic alternating nystagmus. Brain 134: 892–902. PubMed ID: 21303855
- Thomas MG, Thomas S, Kumar A, Proudlock FA, Gottlob I. 1993. FRMD7-Related Infantile Nystagmus. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle,. PubMed ID: 20301748
- Watkins RJ, Patil R, Goult BT, Thomas MG, Gottlob I, Shackleton S. 2013. A novel interaction between FRMD7 and CASK: evidence for a causal role in idiopathic infantile nystagmus. Human Molecular Genetics 22: 2105–2118. PubMed ID: 23406872
- Zhang X, Ge X, Yu Y, Zhang Y, Wu Y, Luan Y, Sun J, Qu J, Jin Z-B, Gu F. 2014. Identification of Three Novel Mutations in the FRMD7 Gene for X-linked Idiopathic Congenital Nystagmus. Scientific Reports 4: PubMed ID: 24434814
- Zhu Y, Zhuang J, Ge X, Zhang X, Wang Z, Sun J, Yang J, Gu F. 2013. Identifcation of a Novel Mutation p.I240T in the FRMD7 gene in a Family with Congenital Nystagmus. Scientific Reports 3: PubMed ID: 24169426
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
Loading...
×
ORDER OPTIONS
View Ordering Instructions1) Select Test Type
2) Select Additional Test Options
No Additional Test Options are available for this test.