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Macular Corneal Dystrophy (MCD) via the CHST6 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
9239 CHST6 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9239CHST681479 81479,81479 $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.

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 backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

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

For Sanger Sequencing click here.

Turnaround Time

18 days on average for standard orders or 13 days 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

Macular corneal dystrophy (MCD) is a rare corneal disorder, which is due to the inability to catabolize corneal keratan sulfate (KS) that leads to slowly progressive visual impairment (Klintworth and Smith 1977; Lewis et al. 2000; Di Iorio et al. 2010). Clinically, MCD is characterized by abnormal opaque deposits in the corneal stroma, keratocytes, posterial region of Descemet's membrane, and endothelium that results in corneal clouding (Klintworth and Smith 1977; Akama et al. 2000). MCD is evident in the first decade of life (El-Ashry et al. 2002). MCD has been classified into three immunophenotypes: MCD I (Hurler syndrome), MCD II (Hunter syndrome) and MCD IA, which are based on the serum level of sulfated keratan sulfate (KS) and immunoreactivity of the corneal tissue (Klintworth and Smith 1977). All these subtypes have similar clinical phenotype (Akama et al. 2000). 

Genetics

Autosomal recessive MCD type I, IA and II are all localized to the same chromosomal region 16q22. Pathogenic variants in the CHST6 (carbohydrate sulfotransferase 6) gene that is located on chromosome 16q22 has shown to be causative for MCD type I, IA and II which are reported to be allelic disorders (Liu et al. 1998). CHST6 encodes a corneal-specific enzyme called glucosamine N-acetyl-6-sulfotransferase (C-GlcNac-6-ST), which is important for the KS proteoglycan (lumican, keratocan, and mimecan) catabolism that is in turn essential for the maintenance of corneal transparency and vision (Di Iorio et al. 2010). Corneal development is influenced by the degree of KS sulfation. Unsulfated KS is observed in the corneas of MCD patients (Lewis et al. 2000; Nakazawa et al. 1984). Missense mutations in CHST6 were reported in patients with MCD type I and type IA, whereas in MCD type II, deletions and/or rearrangements in the upstream region of CHST6 have been reported. However, missense variants were also reported to be causative for MCD type II (Akama et al. 2000; Aldave et al. 2004). Over 150 CHST6 sequence variants (missense, small deletions/duplications, gross deletions and complex genomic rearrangements) have been reported to be causative.

Clinical Sensitivity - Sequencing with CNV PGxome

CHST6 mutation screening in MCD patients from three different studies identified CHST6 pathogenic variants in all affected individuals, which were not present in the control chromosomes (Akama et al. 2000; El-Ashry et al. 2002; Aldave et al. 2004).

Testing Strategy

This test provides full coverage of all coding exons of the CHST6 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

Patients with abnormal corneal opacity or corneal clouding are candidates. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in CHST6.

Gene

Official Gene Symbol OMIM ID
CHST6 605294
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Macular Corneal Dystrophy Type I AR 217800

Citations

  • Akama TO, Nishida K, Nakayama J, Watanabe H, Ozaki K, Nakamura T, Dota A, Kawasaki S, Inoue Y, Maeda N, Yamamoto S, Fujiwara T, Thonar EJ, Shimomura Y, Kinoshita S, Tanigami A, Fukuda MN. 2000. Macular corneal dystrophy type I and type II are caused by distinct mutations in a new sulphotransferase gene. Nature genetics 26: 237–241. PubMed ID: 11017086
  • Aldave AJ, Yellore VS, Thonar EJ, Udar N, Warren JF, Yoon MK, Cohen EJ, Rapuano CJ, Laibson PR, Margolis TP, Small K. 2004. Novel mutations in the carbohydrate sulfotransferase gene (CHST6) in American patients with macular corneal dystrophy. Am. J. Ophthalmol. 137: 465–473. PubMed ID: 15013869
  • Di Iorio E, Barbaro V, Volpi N, Bertolin M, Ferrari B, Fasolo A, Arnaldi R, Brusini P, Prosdocimo G, Ponzin D, Ferrari S. 2010. Localization and expression of CHST6 and keratan sulfate proteoglycans in the human cornea. Exp. Eye Res. 91: 293–299. PubMed ID: 20537995
  • El-Ashry MF, El-Aziz MMA, Wilkins S, Cheetham ME, Wilkie SE, Hardcastle AJ, Halford S, Bayoumi AY, Ficker LA, Tuft S, Bhattacharya SS, Ebenezer ND. 2002. Identification of novel mutations in the carbohydrate sulfotransferase gene (CHST6) causing macular corneal dystrophy. Investigative ophthalmology & visual science 43: 377–382. PubMed ID: 11818380
  • Klintworth GK, Smith CF. 1977. Macular corneal dystrophy: studies of sulfated glycosaminoglycans in corneal explant and confluent stromal cell cultures. The American journal of pathology 89: 167. PubMed ID: 143892
  • Lewis D, Davies Y, Nieduszynski IA, Lawrence F, Quantock AJ, Bonshek R, Fullwood NJ. 2000. Ultrastructural localization of sulfated and unsulfated keratan sulfate in normal and macular corneal dystrophy type I. Glycobiology 10: 305–312. PubMed ID: 10704529
  • Liu N-P, Baldwin J, Lennon F, Stajich JM, Thonar EJA, Pericak-Vance MA, Klintworth GK, Vance JM. 1998. Coexistence of macular corneal dystrophy types I and II in a single sibship. British journal of ophthalmology 82: 241–244. PubMed ID: 9602619
  • Nakazawa K, Hassell JR, Hascall VC, Lohmander LS, Newsome DA, Krachmer J. 1984. Defective processing of keratan sulfate in macular corneal dystrophy. Journal of Biological Chemistry 259: 13751–13757. PubMed ID: 6238957

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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

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