Peters Plus Syndrome via the B3GALTL/B3GLCT 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
8095 B3GLCT 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8095B3GLCT81479 81479(x2) $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

Peters plus syndrome (PpS) is a rare, autosomal recessive, congenital disorder. It is characterized as Peters anomaly along with short stature, brachydactyly and dysmorphic facial features such as a broad nasal tip, malformed and prominent ears, cleft lip and palate (De Almeida et al. 1991; Camera et al. 1994; Maillette de Buy Wenniger-Prick and Hennekam 2002). Peters anomaly (PA) is a birth defect of the anterior segment of the eye (central corneal clouding, thinning of the posterior aspect of the cornea and iridolenticulocorneal adhesions) that can be associated with other systemic malformations (cardiac, genito-urinary and/or central nervous system) (De Almeida et al. 1991; Camera et al. 1993). Approximately 80% of PpS affected children have variable degrees of mental retardation. However, some adults have normal cognitive function (Lesnik Oberstein et al. 1993; Maillette de Buy Wenniger-Prick and Hennekam 2002). An increased loss of fetal death has been reported in families with PpS, which may indicate intrauterine death of some fetuses affected by PpS (Hennekam et al. 1993). Also, congenital hypothyroidism may represent an under-recognized feature of PpS (Kosaki et al. 2006).

Genetics

Peters plus syndrome is an autosomal recessive disorder caused by mutations in B3GALTL (B3GLCT). B3GLCT (β-1,3- glucosyltransferase-like gene), located on chromosome 13q12.3 has been reported as the only causative gene for PpS (Reis et al. 2008). B3GLCT encodes the enzyme β-1,3- glucosyltransferase, which catalyzes the attachment of a glucose moiety to O-linked fucose, forming a rare glucose- β-1,3-fucose disaccharide. This modification is specific to thrombospondin type 1 repeats (TSRs), which are small cysteine-rich motifs found in secreted and cell-surface proteins. TSR proteins have a role in cell-cell and cell-matrix interactions and signaling (Leonhard-Melief and Haltiwanger 2010; Heinonen and Maki 2009). The B3GLCT transcripts were shown to be expressed in numerous human tissues, predominantly heart, kidney, and brain (Heinonen et al. 2006). Mutations in B3GLCT might lead to abnormal glycosylation; hence, PpS is considered a new congenital disorder of glycosylation (CDGs), which also suggests that glycosylation plays a critical role in the development of eye anterior segment (Lesnik Oberstein et al. 2006). However, no functional glycosylation tests have been performed in PpS affected patients (Hess et al. 2008). So far, a variety of about 10 mutations have been reported in the B3GLCT gene that are involved with autosomal recessive PpS (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

A mutation analysis in B3GLCT identified mutations in 100% of the PpS patient cohort (20/20). Among those, 75% were homozygous for the c.660 + 1G > A mutation (Lesnik Oberstein et al. 2006; Reis et al. 2008). Gross B3GLCT deletions have also been reported in PpS patients (Human Gene Mutation Database). Another study reported a 781 kb heterozygous deletion (which involved five genes, including B3GLCT) in one PpS patient, who also carried the common c.660 + 1G > A mutation (Haldeman-Englert et al. 2009).

Testing Strategy

This test provides full coverage of all coding exons of the B3GLCT 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 Peters plus syndrome are candidates. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in B3GLCT.

Gene

Official Gene Symbol OMIM ID
B3GLCT 610308
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Peters Plus Syndrome AR 261540

Citations

  • Camera G, Centa A, Pozzolo S, Camera A. 1993. Peters’-Plus syndrome with agenesis of the corpus callosum: report of a case and confirmation of autosomal recessive inheritance. Clin. Dysmorphol. 2: 317–321. PubMed ID: 8305962
  • Camera G, Pozzolo S, Carta M, Righi E. 1994. Peters’-Plus syndrome: report on an unusual case. Pathologica 86: 673–675. PubMed ID: 7617402
  • De Almeida JC, Reis DF, Júnior JL, Neto JB, Pontes RL, Middleton S, Telles LF. 1991. Short stature, brachydactyly, and Peters’ anomaly (Peters’-plus syndrome): confirmation of autosomal recessive inheritance. Journal of medical genetics 28: 277–279. PubMed ID: 1856836
  • Haldeman-Englert CR, Naeem T, Geiger EA, Warnock A, Feret H, Ciano M, Davidson SL, Deardorff MA, Zackai EH, Shaikh TH. 2009. A 781-kb deletion of 13q12.3 in a patient with Peters plus syndrome. American Journal of Medical Genetics Part A 149A: 1842–1845. PubMed ID: 19610101
  • Heinonen TYK, Maki M. 2009. Peters’-plus syndrome is a congenital disorder of glycosylation caused by a defect in the beta1,3-glucosyltransferase that modifies thrombospondin type 1 repeats. Ann. Med. 41: 2–10. PubMed ID: 18720094
  • Heinonen TYK, Pelto-Huikko M, Pasternack L, Mäki M, Kainulainen H. 2006. Murine ortholog of the novel glycosyltransferase, B3GTL: primary structure, characterization of the gene and transcripts, and expression in tissues. DNA Cell Biol. 25: 465–474. PubMed ID: 16907644
  • Hennekam RC, Schooneveld MJ Van, Ardinger HH, Den Boogaard MJ Van, Friedburg D, Rudnik-Schoneborn S, Seguin JH, Weatherstone KB, Wittebol-Post D, Meinecke P. 1993. The Peters’-Plus syndrome: description of 16 patients and review of the literature. Clin. Dysmorphol. 2: 283–300. PubMed ID: 7508316
  • Hess D, Keusch JJ, Oberstein SAL, Hennekam RCM, Hofsteenge J. 2008. Peters Plus Syndrome Is a New Congenital Disorder of Glycosylation and Involves Defective O-Glycosylation of Thrombospondin Type 1 Repeats. Journal of Biological Chemistry 283: 7354–7360. PubMed ID: 18199743
  • Human Gene Mutation Database (Bio-base).
  • Kosaki R, Kamiishi A, Sugiyama R, Kawai M, Hasegawa T, Kosaki K. 2006. Congenital hypothyroidism in Peters plus syndrome. Ophthalmic Genet. 27: 67–69. PubMed ID: 16754209
  • Leonhard-Melief C, Haltiwanger RS. 2010. O-fucosylation of thrombospondin type 1 repeats. Meth. Enzymol. 480: 401–416. PubMed ID: 20816219
  • Lesnik Oberstein SA, Belzen M van, Hennekam R. 1993. Peters Plus Syndrome. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle,. PubMed ID: 20301637
  • Lesnik Oberstein SAJ, Kriek M, White SJ, Kalf ME, Szuhai K, Dunnen JT den, Breuning MH, Hennekam RCM. 2006. Peters Plus syndrome is caused by mutations in B3GALTL, a putative glycosyltransferase. Am. J. Hum. Genet. 79: 562–566. PubMed ID: 16909395
  • Maillette de Buy Wenniger-Prick LJJM, Hennekam RCM. 2002. The Peters’ plus syndrome: a review. Ann. Genet. 45: 97–103. PubMed ID: 12119218
  • Reis LM, Tyler RC, Abdul-Rahman O, Trapane P, Wallerstein R, Broome D, Hoffman J, Khan A, Paradiso C, Ron N, Bergner A, Semina EV. 2008. Mutation analysis of B3GALTL in Peters Plus syndrome. American Journal of Medical Genetics Part A 146A: 2603–2610. PubMed ID: 18798333

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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