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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 GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
SLC4A11 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7829SLC4A1181479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.

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.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Dana Talsness, PhD

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.

Gene

Official Gene Symbol OMIM ID
SLC4A11 610206
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

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: 41424145. PubMed ID: 19369245
  • Bonanno JA. 2012. Molecular mechanisms underlying the corneal endothelial pump. Experimental Eye Research 95: 27. 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: 14. 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: 700708. 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: 16941706. 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: 29552963. 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: 13271332. 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: 755757. 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

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

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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