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Lujan Syndrome, FG Syndrome Type 1 and Ohdo Syndrome via the MED12 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
7991 MED12 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7991MED1281479 81479(x2) $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

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

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

  • Anthony Krentz, PhD

Clinical Features and Genetics

Clinical Features

Lujan Syndrome (LS; also known as Lujan-Fryns Syndrome) and FG Syndrome Type 1 (FGS1; also known as Opitz-Kaveggia Syndrome) are allelic disorders with overlapping clinical phenotypes. LS and FGS1 share the clinical findings of cognitive impairment and hypotonia (Lyons et al. J Med Genet 46:9-13, 2009). However, LS is further characterized by a Marfan-like appearance, which include a marfanoid habitus (large head; tall, thin body habitus) and craniofacial changes (long, thin face; high nasal root; high, narrow palate; and short philtrum) (Lujan. Am J Med Genet 17:311-322, 1984; Schwartz et al. J Med Genet 44:472-477, 2007). Conversely, FGS1 is further characterized by constipation, anal anomalies, small and simple ears, tall and prominent forehead, downslanting palpebral fissures, broad thumbs and halluces, and abnormalities of the corpus callosum (Opitz et al. Z Kinderheilkd. 117:1-18, 1974; Risheg et al. Nat Genet 39:451-453, 2007). LS has overlapping clinical features with Loeys-Dietz syndrome (LDS, OMIM 609192; 608967; 610380; 610168), Shprintzen-Goldberg syndrome (OMIM# 182212), Fragile X syndrome (OMIM 300624) and Snyder-Robinson syndrome (OMIM 309583). FGS1 has overlapping clinical features with alpha-thalasemia X-linked mental retardation syndrome (ATRX; OMIM 301040), Coffin-Lowry syndrome (OMIM 303600), Rubinstein-Taybi syndrome (OMIM 180849) and Fragile X syndrome (OMIM 300624). Maat-Kievit-Brunner (MKB) type Ohdo syndrome is characterized by intellectual disability and distinctive facial features, which include blepharophimosis, ptosis, a long philtrum and a narrow mouth. The facial features become more pronounced and the face becomes more triangular as the individual ages (Maat-Kievit et al. Am J Med Genet 47:901-906, 1993).

Genetics

LS, FGS1 and Ohdo syndrome, MKB type are inherited in an X-linked recessive manner. LS syndrome is caused by a c.3020A>G (p.Asn1007Ser) mutation in exon 22 of the MED12 gene (Schwartz et al. J Med Genet 44:472-477, 2007). FG syndrome is caused by a c.2881C>T (p.Arg961Trp) mutation or a c.2873G>A (p.Gly958Glu) mutation in exon 21 of MED12 (Risheg et al Nat Genet 39:451-453, 2007; Rump et al. Clin Genet 79:183-188, 2011). Three different missense mutations in MED12 have been found in individuals with Ohdo syndrome, MKB type (Vulto-van Silfhout et al. Am J Med Genet 92:401-406, 2013). MED12 encodes for the mediator of RNA polymerase II transcription subunit 12, which serves as an interface between transcription factors and RNA polymerase II. The mediator complex comprises 25 subunits organized into four modules. The MED12 protein is part of the module needed for repression of transcription (Zhou et al. Mol Cell Biol 26:8667-8682, 2006; Philibert and Madan. Pharmacogenomics 8:909-916, 2007).

Clinical Sensitivity - Sequencing with CNV PG-Select

The prevalence of FGS, LS and Ohdo syndrome, MKB type is unknown. MED12 mutations have been identified in approximately 13% of individuals clinically diagnosed with FGS (Risheg et al. Nat Genet 39(4): 451-453, 2007).

Deletion/duplication mutations in MED12 are not known to cause Lujan, FG or Ohdo syndrome, MKB type. No gross deletions/duplications have been reported in MED12 (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the MED12 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for this test are male patients with symptoms consistent with FG, LS and Ohdo syndrome, MKB type and family members of patients who have known MED12 mutations.

Gene

Official Gene Symbol OMIM ID
MED12 300188
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
Opitz G/BBB Syndrome Panel

Citations

  • Human Gene Mutation Database (Bio-base).
  • Lujan, J. E., et.al. (1984). "A form of X-linked mental retardation with marfanoid habitus." Am J Med Genet 17(1): 311-22. PubMed ID: 6711603
  • Lyons, M. J., et.al. (2009). "Clinical experience in the evaluation of 30 patients with a prior diagnosis of FG syndrome." J Med Genet 46(1): 9-13. PubMed ID: 18805826
  • Maat-Kievit et al. (1993) "Two additional cases of the Ohdo blepharophimosis syndrome" Am J Med Genet 47:901-906. PubMed ID: 8279489
  • Opitz, J. M., Kaveggia, E. G. (1974). "Studies of malformation syndromes of man 33: the FG syndrome. An X-linked recessive syndrome of multiple congenital anomalies and mental retardation." Z Kinderheilkd 117(1): 1-18. PubMed ID: 4365204
  • Philibert, R. A., and┬áMadan, A. (2007). "Role of MED12 in transcription and human behavior." Pharmacogenomics 8(8): 909-916. PubMed ID: 17716226
  • Risheg, H., et.al. (2007). "A recurrent mutation in MED12 leading to R961W causes Opitz-Kaveggia syndrome." Nat Genet 39(4): 451-453. PubMed ID: 17334363
  • Rump et al. (2011) "A novel mutation in MED12 causes FG syndrome (Opitz-Kaveggia syndrome)." Clin Genet 79:183-188. PubMed ID: 20507344
  • Schwartz, C. E., et.al. (2007). "The original Lujan syndrome family has a novel missense mutation (p.N1007S) in the MED12 gene." J Med Genet 44(7): 472-477. PubMed ID: 17369503
  • Vulto-van Silfhout et al. (2013) "Mutations in MED12 cause X-linked Ohdo syndrome." Am J Med Genet 92: 401-406. PubMed ID: 23395478
  • Zhou, H., et.al. (2006). "Mediator modulates Gli3-dependent Sonic hedgehog signaling." Mol Cell Biol 26(23): 8667-82. PubMed ID: 17000779

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

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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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