Townes-Brocks Syndrome via the SALL1 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
8227 SALL1 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8227SALL181479 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

Townes-Brocks syndrome (TBS, OMIM#107480) is a multiple malformation syndrome characterized by the triad of imperforate anus, dysplastic ears frequently associated with sensorineural or conductive hearing impairment, and thumb malformations (triphalangeal thumbs, preaxial polydactyly, hypoplastic thumbs) without shortening of the radius. Foot malformations (flat feet, overlapping toes) and genitourinary malformations are also common. Renal impairment including end-stage renal disease, congenital heart disease, and mental retardation may occur (Kohlhase. GeneReviews. 2007).

Genetics

Townes-Brocks syndrome (TBS) is inherited in an autosomal dominant manner. Penetrance seems complete, but expressivity is highly variable. SALL1 is the only gene known to be associated with TBS; about half of cases are caused by de novo variants. SALL1 encodes sal-like protein 1, a C2H2 zinc finger transcription factor of the SAL type. Sal-like protein 1 appears to be an essential developmental regulator, which interacts with SALL4 and is regulated by TBX5 (Harvey&Logan Development 133:1165–1173, 2006). The majority of reported variants in SALL1 are nonsense and frameshift variants that positioned in exon 2 of the gene and resulted in premature stop codons. Both haploinsufficiency and dominant-negative effects of mutated SALL1 protein have been proposed for the pathogenesis of TBS (Kohlhase GeneReviews 2007; Maquat et al. Nat Rev Mol Cell Biol 5:89–99, 2004; Borozdin et al. Hum Mutat 27:211–212, 2006; Kiefer et al. Hum Mol Genet. 12:2221–2227, 2003).

Clinical Sensitivity - Sequencing with CNV PGxome

Sequencing of SALL1 is predicted to detect disease variants in up to 70% of individuals with the classic triad of malformations (Kohlhase GeneReviews 2007; Kohlhase et al. Am J Hum Genet 64:435-445, 1999; Marlin et al. Hum Mutat 14:377-386, 1999). Large deletions involving single or multiple exons have been reported to account for less than 5% cases (Borozdin et al. Hum Mutat 27:211-212, 2006); such deletions are generally not detected by sequence analysis.

Testing Strategy

This test provides full coverage of all coding exons of the SALL1 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 this test are patients with clinical features consistent with Townes-Brocks syndrome and family members of patients who have known SALL1 variants.

Gene

Official Gene Symbol OMIM ID
SALL1 602218
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Townes-Brocks Syndrome AD 107480

Citations

  • Borozdin, W., et.al. (2006). "Detection of heterozygous SALL1 deletions by quantitative real time PCR proves the contribution of a SALL1 dosage effect in the pathogenesis of Townes-Brocks syndrome." Hum Mutat 27(2): 211-2. PubMed ID: 16429401
  • Harvey, S. A., Logan, M. P. (2006). "sall4 acts downstream of tbx5 and is required for pectoral fin outgrowth." Development 133(6): 1165-73. PubMed ID: 16501170
  • Kiefer, S. M., et.al. (2003). "Expression of a truncated Sall1 transcriptional repressor is responsible for Townes-Brocks syndrome birth defects." Hum Mol Genet 12(17): 2221-7. PubMed ID: 12915476
  • Kohlhase (2007). "Townes-Brocks Syndrome." PubMed ID: 20301618
  • Kohlhase, J., et.al. (1999). "Molecular analysis of SALL1 mutations in Townes-Brocks syndrome." Am J Hum Genet 64(2): 435-45. PubMed ID: 9973281
  • Maquat, L. E. (2004). "Nonsense-mediated mRNA decay: splicing, translation and mRNP dynamics." Nat Rev Mol Cell Biol 5(2): 89-99. PubMed ID: 15040442
  • Marlin, S., et.al. (1999). "Townes-Brocks syndrome: detection of a SALL1 mutation hot spot and evidence for a position effect in one patient." Hum Mutat 14(5): 377-86. PubMed ID: 10533063

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

View Ordering Instructions

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.

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