X-linked Megalocornea 1 (MGC1) via the CHRDL1 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
8361 CHRDL1 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8361CHRDL181479 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.

For Reflex to PGxome pricing click here.

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 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View 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

Clinical Features and Genetics

Clinical Features

X-linked megalocornea (MGC1) is a nonprogressive bilateral anterior segment dysgenesis of the eye with normal anterior chamber angles, intraocular pressure and axial lengths. This indicates that megalocornea and primary congenital glaucoma are two distinct clinical entities (Kraft et al. 1984; Ho and Walton 2004). However, the MGC1 patients have an increased risk of developing glaucoma (Meire and Delleman 1992). MGC1 is clinically characterized by increased bilateral cornea diameter (greater than 12.5 mm) and a deep anterior chamber, which is evident at birth, and later onset of mosaic corneal degeneration (shagreen), corneal arcus juvenilis, and presenile cataracts (Mackey et al. 1991; Meire et al. 1991). Secondary complications include astigmatic refractive errors, miosis, atrophy of the iris stroma, iridodonesis, and subluxation of the lens (Webb et al. 2012).

Genetics

Chordin-like 1 gene (CHRDL1) on Xq21.3-q22 (Chen et al. 1989; Meire et al. 1991) is reported to be the only causative gene for X- linked MGC1 (Webb et al. 2012). Female carriers are often asymptomatic (Mackey et al. 1991). CHRDL1 encoded protein ventroptin is shown to be expressed in the developing human cornea and anterior segment of the eye, in addition to the retina, and is required for anterior segment development (Webb et al. 2012). Ventroptin, which is a bone morphogenic protein (BMP) antagonist regulates Bmp4 and Bmp2 signaling the in developing retina and brain and is proposed to have a role in specification of topographic retinotectal projections. Regulation of BMP has been shown to be important for both patterning and control of organ size during embryogenesis (Webb et al. 2012). So far, less than 10 pathogenic sequence variations (including missense, nonsense, splicing, small and gross deletions) in CHRDL1 have been reported in X-linked megalocornea (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

Assessment of the X-Linked Megalocornea (MGC1) phenotype in six families showed that all affected male individuals carried mutations in CHRDL1 and female carriers did not show any clinical signs of MGC1. None of the CHRDL1 mutations were detected in 220 control X chromosomes (Webb et al. 2012). Another screening also identified CHRDL1 mutations in all MGC1 affected male individuals and in the heterozygous state in their mother, which was not present in an unaffected brother or in unrelated controls (Han et al. 2013).

Testing Strategy

This test provides full coverage of all coding exons of the CHRDL1 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.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

All patients with symptoms suggestive of X-linked megalocornea, and relatives of patients with known CHRDL1 mutations.

Gene

Official Gene Symbol OMIM ID
CHRDL1 300350
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Megalocornea 1, X-linked 309300

Citations

  • Chen JD, Mackey D, Fuller H, Serravalle S, Olsson J, Denton MJ. 1989. X-linked megalocornea: close linkage to DXS87 and DXS94. Hum. Genet. 83: 292–294. PubMed ID: 2571565
  • Han J, Young JW, Frausto RF, Isenberg SJ, Aldave AJ. 2013. X-linked Megalocornea Associated with the Novel CHRDL1 Gene Mutation p.(Pro56Leu*8). Ophthalmic Genet. PubMed ID: 24073597
  • Ho CL, Walton DS. 2004. Primary megalocornea: clinical features for differentiation from infantile glaucoma. J Pediatr Ophthalmol Strabismus 41: 11–17; quiz 46–47. PubMed ID: 14974829
  • Human Gene Mutation Database (Bio-base).
  • Kraft SP, Judisch GF, Grayson DM. 1984. Megalocornea: a clinical and echographic study of an autosomal dominant pedigree. J Pediatr Ophthalmol Strabismus 21: 190–193. PubMed ID: 6389819
  • Mackey DA, Buttery RG, Wise GM, Denton MJ. 1991. Description of X-linked megalocornea with identification of the gene locus. Arch. Ophthalmol. 109: 829–833. PubMed ID: 2043071
  • Meire FM, Bleeker-Wagemakers EM, Oehler M, Gal A, Delleman JW. 1991. X-linked megalocornea. Ocular findings and linkage analysis. Ophthalmic Paediatr Genet 12: 153–157. PubMed ID: 1754164
  • Meire FM, Delleman JW. 1992. Autosomal dominant congenital miosis with megalocornea. Ophthalmic Paediatr Genet 13: 123–129. PubMed ID: 1495762
  • Webb TR, Matarin M, Gardner JC, Kelberman D, Hassan H, Ang W, Michaelides M, Ruddle JB, Pennell CE, Yazar S, Khor CC, Aung T, et al. 2012. X-linked megalocornea caused by mutations in CHRDL1 identifies an essential role for ventroptin in anterior segment development. Am. J. Hum. Genet. 90: 247–259. PubMed ID: 22284829

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.

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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ORDER OPTIONS

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