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Meesmann Corneal Dystrophy (MCD) via the KRT12 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
8387 KRT12 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8387KRT1281479 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.

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

Corneal dystrophies (CDs) are rare inherited disorders. Clinically, CDs are characterized as loss of corneal transparency and impaired refraction, which may be caused by a progressive accumulation of deposits (which can be amyloid, hyaline or a combination) on different layers of the cornea. With disease progression, visual acuity gradually decreases and can lead to visual impairment (Correa-Gomez et al. 2007; Klintworth 2009). CDs are non-inflammatory corneal diseases that are classified into three groups based on the sole or predominant anatomical location of the deposits. The three groups are anterior CDs, stromal CDs and posterior CDs. Most CDs exhibit autosomal dominant inheritance with a high degree of penetration. However, CDs present marked inter-and intra-familial variation in clinical expressivity (Klintworth 2009; Munier et al. 2002). CDs are typically evident in first or second decades of life, and manifestations are restricted to the cornea (Zenteno et al. 2006; Klintworth 2009).

Meesmann corneal dystrophy (MCD) is characterized by fragile corneal epithelium and intraepithelial microcyst formation. MCD is generally mild and affected individuals are often asymptomatic while some suffer from recurrent erosions leading to lacrimation, photophobia, and deterioration in visual acuity (Szaflik et al. 2008).

Genetics

Corneal dystrophies (CDs) are genetically heterogeneous. Autosomal dominant and autosomal recessive Mendelian modes of inheritance have been reported. Different types of corneal dystrophies are caused by pathogenic variants in the AGBL1, CHST6, COL8A2, KRIT3, DCN, KRT12, PIKFYVE, SLC4A11, TACSTD2, TGFBI, UBIAD1, VSX1 and ZEB1 genes (Poulaki and Colby 2008; Klintworth 2009; Riazuddin et al. 2010; Riazuddin et al. 2013; Bredrup et al. 2005). CHST6 and TACSTD2 pathogenic variants cause autosomal recessive CDs.

Dominant-negative variants in KRIT3 and KRT12 cause dominant Meesmann corneal dystrophy (MCD) (Allen et al. 2016). KRT12 encoded Keratin 12 is an intermediate-filament protein expressed specifically in corneal epithelium (Nishida et al. 1997). Nishida et al. showed that the pathogenic variants found in their cohort were either in the highly conserved alpha-helix-initiation motif of rod domain 1A or in the alpha-helix-termination motif of rod domain 2B, which are essential for keratin filament assembly (Nishida et al. 1997). To date, over 20 causative variants have been reported (Human Gene Mutation Database). Nearly all of these are missense; no pathogenic premature termination variants have been reported to date.

Clinical Sensitivity - Sequencing with CNV PGxome

Due to genetic heterogeneity of corneal dystrophy (CD), estimating the clinical sensitivity for some genes is difficult. A mutation spectrum analysis identified TGFBI pathogenic variants in 80% (50/61) of corneal dystrophy patients (Munier et al. 2002). A mutation screening in 26 affected members of 20 Japanese Gelatinous drop-like corneal dystrophy families identified TACSTD2 pathogenic variants in all 26 individuals. A founder mutation c.352C>T(p.Gln118*) was found in 33 out of 40 (82.5%) disease alleles (Tsujikawa et al. 1999). These studies indicate that pathogenic variants in KRT12 are not a common cause of CDs.

Testing Strategy

This test provides full coverage of all coding exons of the KRT12 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 Meesmann corneal dystrophy are candidates.

Gene

Official Gene Symbol OMIM ID
KRT12 601687
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Meesmann Corneal Dystrophy AD 122100

Related Tests

Name
TGFBI-Associated Corneal Dystrophies via the TGFBI Gene
Congenital Hereditary Endothelial Dystrophy Type 2 (CHED2) and Harboyan Syndrome via the SLC4A11 Gene
Gelatinous Drop-Like Corneal Dystrophy (GDLD) via the TACSTD2 Gene
Keratoconus and Posterior Polymorphous Corneal Dystrophy via the VSX1 Gene
Macular Corneal Dystrophy (MCD) via the CHST6 Gene
Schnyder Crystalline Corneal Dystrophy (SCCD) via the UBIAD1 Gene

Citations

  • Allen E.H. et al. 2016. Human Molecular Genetics. 25: 1176-91. PubMed ID: 26758872
  • Bredrup et al. 2005. PubMed ID: 15671264
  • Correa-Gomez et al. 2007. PubMed ID: 17893671
  • Human Gene Mutation Database (Bio-base).
  • Klintworth. 2009. PubMed ID: 19236704
  • Munier et al. 2002. PubMed ID: 11923233
  • Nishida K. et al. 1997. American Journal of Human Genetics. 61: 1268-75. PubMed ID: 9399908
  • Poulaki and Colby. 2008. PubMed ID: 18214787
  • Riazuddin et al. 2010. PubMed ID: 20036349
  • Riazuddin et al. 2013. PubMed ID: 24094747
  • Szaflik J.P. et al. 2008. Molecular Vision. 14: 1713-8. PubMed ID: 18806880
  • Tsujikawa et al. 1999. PubMed ID: 10192395
  • Zenteno et al. 2006. PubMed ID: 16636649

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.
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