Meckel-Gruber Syndrome / Joubert Syndrome via the TCTN2 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesPrice Test CPT CodeGene CPT Codes Copy CPT Codes
11041 TCTN2$890 8147981479,81479 Add to Order

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.

For Reflex to PGxome pricing click here.

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

For Sanger Sequencing click here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Meckel-Gruber Syndrome (MKS; OMIM 249000) is the most common form of syndromic neural tube defect. MKS is characterized by occipital encephalocele, polycystic kidneys, and postaxial polydactyly (Alexiev et al. Arch Pathol Lab Med 130:1236-1238, 2006). MKS is a common cause of prenatal echogenic kidneys (Chaumoitre et al. Ultrasound Obstet Gynecol 28:911-917, 2006). Nearly all MKS infants are stillborn or die shortly after birth. Joubert syndrome (JS; OMIM 213300) is marked by ataxia, hypotonia, abnormal eye movements, apraxia, neonatal respiratory anomalies, mental retardation, agenesis/hypoplasia of the cerebellar vermis, and a brain malformation known as the "molar tooth sign" (MTS) on cranial MRI. MTS is considered to be the most characteristic diagnostic feature. JS patients have substantial phenotypic variation. Some JS patients develop retinal dystrophy and/or progressive renal failure.

Genetics

Both MKS and Joubert syndrome exhibit autosomal recessive inheritance. Both disorders have high levels of locus heterogeneity. Mutations in the TCTN2 gene were reported to cause MKS8 and Joubert syndrome (Shaheen et al. Hum Mut 32:573, 2011; Sang et al. Cell 145:513, 2011). The TCTN2 gene encodes the Tectonic 2 protein (TCTN2), which is predicted to interact with MKS1 protein and to regulate hedgehog-dependent neural tube patterning (Shaheen et al. 2011; Sang et al. 2011). Furthermore, Tctn2 null-mouse demonstrates that Tctn2 protein is required for ciliogenesis (Shaheen et al. 2011; Sang et al. 2011; Garcia-Gonzalo et al. Nat Genet 43:776, 2011). A mix of nonsense, splicing, and frameshift mutations have been reported in the TCTN2 gene (Shaheen et al. 2011; Sang et al. 2011).

Testing Strategy

This test provides full coverage of all coding exons of the TCTN2 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).

Clinical Sensitivity - Sequencing with CNV

The prevalence of the TCTN2 mutations is currently unknown.

Indications for Test

Candidates for this test are patients with symptoms consistent with MKS or Joubert syndrome and family members of patients. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in TCTN2.

Gene

Official Gene Symbol OMIM ID
TCTN2 613846
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Meckel Syndrome 8 AR 613885

Citations

  • Alexiev BA, Lin X, Sun CC, Brenner DS. 2006. Meckel-Gruber syndrome: pathologic manifestations, minimal diagnostic criteria, and differential diagnosis. Arch. Pathol. Lab. Med. 130: 1236-1238. PubMed ID: 16879033
  • Chaumoitre K, Brun M, Cassart M, Maugey-Laulom B, Eurin D, Didier F, Avni EF. 2006. Differential diagnosis of fetal hyperechogenic cystic kidneys unrelated to renal tract anomalies: A multicenter study. Ultrasound Obstet Gynecol 28: 911–917. PubMed ID: 17094077
  • Garcia-Gonzalo, F. R., et.al. (2011). PubMed ID: 21725307
  • Sang, L., et.al. (2011). PubMed ID: 21565611
  • Shaheen, R., et.al. (2011). PubMed ID: 21462283

Ordering/Specimens

Ordering Options

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.

Specimen Types

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