X-linked Cleft Palate via the TBX22 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
12089 TBX22 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
12089TBX2281479 81479 $890 Order Options and Pricing

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing 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

Pathogenic variants in the TBX22 gene are associated with X-linked cleft palate (CPX) and Abruzzo-Erickson syndrome. CPX is a non-syndromic (isolated) form of cleft palate. The palatal phenotype ranges from a high arched palate, bifid uvula or submucous cleft to complete cleft of the secondary palate (Baybrook et al. 2001. PubMed ID: 11559848; Marcano et al. 2004. PubMed ID: 14729838). Velopharyngeal insufficiency and ankyloglossia may accompany palatal anomalies or occur in isolation. Although CPX predominantly affects males, a proportion of carrier females present with ankyloglossia with or without cleft palate, bifid uvula or velopharyngeal insufficiency (Baybrook et al. 2001. PubMed ID: 11559848; Marcano et al. 2004. PubMed ID: 14729838).

At the other end of the spectrum is Abruzzo-Erickson syndrome, a rare syndromic form of cleft palate. To date, a single multigenerational family with this syndrome has been reported (Abruzzo and Erickson. 1977. PubMed ID: 839509; Pauws et al. 2013. PubMed ID: 22784330). The clinical features of Abruzzo-Erickson syndrome in this family include cleft palate, palatal rugosity, coloboma, malar hypoplasia, large ears, hearing impairment, hypospadias, radioulnar synostosis, wide-spaced second and third fingers, and short stature.

Genetics

CPX and Abruzzo-Erickson syndrome are inherited in an X-linked dominant manner, although the phenotype displays incomplete dominance in females. The clinical phenotype in affected males is the result of complete loss of TBX22 protein function, whilst the clinical phenotype in females is a consequence of haploinsufficiency. Pathogenic frameshift, missense, nonsense, and splice site variants in TBX22 have been reported to cause CPX (Braybrook et al. 2002. PubMed ID: 12374769; Marcano et al. 2004. PubMed ID: 14729838; Pauws et al. 2013. PubMed ID: 22784330). Pathogenic missense variants causing CPX are localized to the highly conserved TBX22 DNA-binding T box domain and likely result in loss of function (Braybrook et al. 2002. PubMed ID: 12374769; Pauws et al. 2009. PubMed: 19648124). A single pathogenic TBX22 splice site variant has been reported to cause Abruzzo-Erickson syndrome (Abruzzo and Erickson. 1977. PubMed ID: 839509; Pauws et al. 2013. PubMed ID: 22784330).

TBX22 encodes the T-box 22 protein. This protein is a T-box-containing transcription factor that is primarily expressed in the palatal shelves and lingual frenulum during palatogenesis in the developing embryo (Braybrook et al. 2002. PubMed ID: 12374769). Studies of TBX22 null mice suggest that loss of TBX22 function results in a failure of palatal osteoblast differentiation and maturation, which reduces ossification and leads to craniofacial anomalies (Pauws et al. 2009. PubMed ID: 19648291).

Clinical Sensitivity - Sequencing with CNV PGxome

Up to 5% of unselected cases with non-syndromic cleft palate may be explained by pathogenic variants in the TBX22 gene (Marcano et al. 2004. PubMed ID: 14729838). The clinical sensitivity increases if individuals are selected based on a positive personal and family history of X-linked cleft palate and ankyloglossia (Braybrook et al. 2001. PubMed ID: 11559848).

Testing Strategy

This test provides full coverage of all coding exons of the TBX22 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

Candidates for testing include individuals with ankyloglossia, cleft palate with or without ankyloglossia or a family history consistent with a familial form of X-linked cleft palate. Individuals with a personal or family history consistent with X-linked Abruzzo-Erickson syndrome may also consider testing.

Gene

Official Gene Symbol OMIM ID
TBX22 300307
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Diseases

Name Inheritance OMIM ID
Abruzzo-Erickson syndrome XL 302905
Cleft Palate X-Linked XL 303400

Citations

  • Abruzzo and Erickson. 1977. PubMed ID: 839509
  • Braybrook et al. 2001. PubMed ID: 11559848
  • Braybrook et al. 2002. PubMed ID: 12374769
  • Marçano et al. 2004. PubMed ID: 14729838
  • Pauws et al. 2009. PubMed ID: 19648291
  • Pauws et al. 2013. PubMed ID: 22784330

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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