Congenital Hereditary Endothelial Dystrophy Type 2 (CHED2) and Harboyan Syndrome via the SLC4A11 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 | |
|---|---|---|---|---|---|
| 7829 | SLC4A11 | 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
Congenital hereditary endothelial dystrophy (CHED) is a rare inherited corneal disorder, which results from hypoplasia or degeneration and dysfunction of the endothelial cells. Clinically, CHED is characterized as bilateral, symmetrical, corneal opacification and nystagmus, without other anterior segment abnormalities. CHED is usually evident at birth or within the neonatal period (Vithana et al. 2006; Hemadevi et al. 2008). CHED is classified into CHED1 and CHED2, which are inherited in autosomal dominant and recessive manner, respectively. CHED1 differs from CHED2 in the age of onset (CHED1 manifests later in the life) and severity (CHED2 is more severe) (Sultana et al. 2007).
Harboyan syndrome (HS) is a rare disorder characterized as CHED accompanied by progressive, postlingual sensorineural deafness (Desir and Abramowicz 2008). The estimated prevalence rate for congenital corneal clouding is ~ 3 in 100,000 newborns. In a study which included 47 congenital corneal abnormalities cases, Peters anomaly accounted for 40% of the cases followed by sclerocornea (18%), limbal dermoid (15%), congenital glaucoma (7%), microphthalmia (4%), birth trauma, and metabolic disease (3%), etc. Genetic testing can be helpful in the differential diagnosis and appropriate treatment (Desir and Abramowicz 2008). Audiometry helps in the differential diagnosis between Harboyan syndrome and CHED2 as they both share the same ocular abnormalities. Corneal transplantation (penetrating keratoplasty) has been reported as definitive treatment (Desir and Abramowicz 2008).
Genetics
CHED2 is inherited in an autosomal recessive manner and is caused by mutations in the SLC4A11 gene. The locus for CHED1 has been mapped to the pericentromeric region of chromosome 20, which is physically and genetically distinct from the CHED2 locus (Hand et al. 1999). SLC4A11, which encodes sodium bicarbonate transporter-like solute carrier family 4 member 11 protein, is expressed in several organs and tissues, including eyes, blood, lungs, ovaries, colon, mouth, embryonic tissue, pancreas, kidneys, skin, cranial nerves, prostate, and brain (Kodaganur et al. 2013). Corneal endothelium acts as barrier between the corneal stroma and the aqueous humor to regulate the water content in the cornea through membrane active transport mechanisms (Bonanno 2012). Loss of function mutations in SLC4A11 lead to the perturbation of the SLC4A11-mediated membrane active transport mechanism which leads to the CHED2 phenotype as well as HS (Aldahmesh et al. 2009). So far, about 85 SLC4A11 mutations (missense, nonsense, splicing, small and gross insertions and deletions) have been reported (Human Gene Mutation Database).
Clinical Sensitivity - Sequencing with CNV PG-Select
A mutation analysis in 25 patients from 20 families (consanguinity was noted in 9 out of 20 families) clinically diagnosed with CHED2 detected SLC4A11 mutations in 56% (14/25) of patients (Paliwal et al. 2010). Another study also identified SLC4A11 mutations in 83% (41/49) of the CHED2 affected patients from 35 families (consanguinity was noted in 23 out of 35 families) (Sultana et al. 2007).
Testing Strategy
This test provides full coverage of all coding exons of the SLC4A11 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.
Indications for Test
All patients with symptoms suggestive of congenital corneal dystrophy are candidates. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in SLC4A11.
All patients with symptoms suggestive of congenital corneal dystrophy are candidates. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in SLC4A11.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| SLC4A11 | 610206 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Diseases
| Name | Inheritance | OMIM ID |
|---|---|---|
| Corneal Dystrophy And Perceptive Deafness | AR | 217400 |
| Corneal Endothelial Dystrophy Type 2 | AR | 217700 |
Citations
- Aldahmesh MA, Khan AO, Meyer BF, Alkuraya FS. 2009. Mutational Spectrum of SLC4A11 in Autosomal Recessive CHED in Saudi Arabia. Investigative Ophthalmology & Visual Science 50: 4142–4145. PubMed ID: 19369245
- Bonanno JA. 2012. Molecular mechanisms underlying the corneal endothelial pump. Experimental Eye Research 95: 2–7. PubMed ID: 21693119
- Desir J, Abramowicz M. 2008. Congenital hereditary endothelial dystrophy with progressive sensorineural deafness (Harboyan syndrome). Orphanet Journal of Rare Diseases 3: 28. PubMed ID: 18922146
- Hand CK, Harmon DL, Kennedy SM, FitzSimon JS, Collum LM, Parfrey NA. 1999. Localization of the gene for autosomal recessive congenital hereditary endothelial dystrophy (CHED2) to chromosome 20 by homozygosity mapping. Genomics 61: 1–4. PubMed ID: 10512674
- Hemadevi B, Veitia RA, Srinivasan M, Arunkumar J, Prajna NV, Lesaffre C, Sundaresan P. 2008. Identification of mutations in the SLC4A11 gene in patients with recessive congenital hereditary endothelial dystrophy. Arch. Ophthalmol. 126: 700–708. PubMed ID: 18474783
- Human Gene Mutation Database (Bio-base).
- Kodaganur SG, Kapoor S, Veerappa AM, Tontanahal SJ, Sarda A, Yathish S, Prakash DR, Kumar A. 2013. Mutation analysis of the SLC4A11 gene in Indian families with congenital hereditary endothelial dystrophy 2 and a review of the literature. Mol Vis 19: 1694–1706. PubMed ID: 23922488
- Paliwal P, Sharma A, Tandon R, Sharma N, Titiyal JS, Sen S, Nag TC, Vajpayee RB. 2010. Congenital hereditary endothelial dystrophy - mutation analysis of SLC4A11 and genotype-phenotype correlation in a North Indian patient cohort. Mol Vis 16: 2955–2963. PubMed ID: 21203343
- Sultana A, Garg P, Ramamurthy B, Vemuganti GK, Kannabiran C. 2007. Mutational spectrum of the SLC4A11 gene in autosomal recessive congenital hereditary endothelial dystrophy. Mol Vis 13: 1327–1332. PubMed ID: 17679935
- Vithana EN, Morgan P, Sundaresan P, Ebenezer ND, Tan DTH, Mohamed MD, Anand S, Khine KO, Venkataraman D, Yong VHK, Salto-Tellez M, Venkatraman A, et al. 2006. Mutations in sodium-borate cotransporter SLC4A11 cause recessive congenital hereditary endothelial dystrophy (CHED2). Nat. Genet. 38: 755–757. PubMed ID: 16767101
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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