Seckel Syndrome, Primary Microcephaly and Familial Cutaneous Telangiectasia and Cancer Syndrome via the ATR Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesPrice Test CPT CodeGene CPT Codes Copy CPT Codes STAT Prenatal
7979 ATR$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.

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

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

Seckel syndrome is a rare autosomal recessive disorder that is characterized by pre- and post-natal growth delay resulting in dwarfism. Other characteristics include microcephaly, mild to moderate mental retardation, characteristic narrow bird-like face with a beak-like nose, large eyes, micrognathia, delayed bone age, hip dysplasia, and elbow dislocation (Faivre et al. 2002). Germline pathogenic mutations in the ATR gene, which is causative for Seckel syndrome, have also been described as causative for primary microcephaly (Verloes et al. 1993; Mokrani-Benhelli et al. 2013). In addition, a germline mutation has also been shown to segregate in a five generation family with autosomal dominant oropharyngeal cancer syndrome/familial cutaneous telangiectasia and cancer syndrome (FCTCS) (Tanaka et al. 2012). Affected individuals displayed telangiectases, alopecia, and other malignancies such as nonmelanoma skin cancer, and less commonly breast cancer and cervical cancer. Interestingly, individuals with primary microcephaly and Seckel syndrome do not display an increased risk of malignancy.

Genetics

Seckel syndrome, primary microcephaly, and FCTCS are disorders that are caused by mutations in the ATR gene (Kalay et al. 2011; Tanaka et al. 2012; Verloes et al. 1993). The ATR gene encodes a serine/threonine-protein kinase which is involved in DNA repair through phosphorylation of proteins (e.g. p53, Rad17, Nbs1 and H2AX) similar to those phosphorylated by the ATM kinase (O’Driscoll et al. 2003). ATM is activated after DNA double-strand breaks, whereas ATR is activated by DNA single strands, such as those that occur during response to stalled replication forks (Tanaka et al. 2012); ATR cell lines from affected individuals exhibit defective DNA damage response (O’Driscoll et al. 2003). Limited reported pathogenic variants include missense, nonsense, splicing, small and large deletions (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the ATR 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 clinical sensitivity of ATR germline mutations in patients with Seckel syndrome, primary microcephaly or familial cutaneous telangiectasia and cancer syndrome is currently unknown as only a small number of individual cases have been reported.

The clinical sensitivity of ATR germline deletions and duplications in patients with Seckel syndrome, primary microcephaly or familial cutaneous telangiectasia and cancer syndrome is currently unknown as only a small number of individual cases have been reported. No large deletions and duplications have been reported for Seckel, syndrome and FCTCS, but a single gross deletion has been reported for primary microcephaly (Mokrani-Benhelli et al. 2013).

Indications for Test

Individuals suspected of having Seckel syndrome, primary microcephaly or familial cutaneous telangiectasia and cancer syndrome. Also individuals with a family history of these disorders. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in ATR.

Gene

Official Gene Symbol OMIM ID
ATR 601215
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
LIG4 Syndrome via the LIG4 Gene

Citations

  • Faivre L, Merrer M Le, Lyonnet S, Plauchu H, Dagoneau N, Campos-Xavier AB, Attia-Sobol J, Verloes A, Munnich A, Cormier-Daire V. 2002. Clinical and genetic heterogeneity of Seckel syndrome. American Journal of Medical Genetics 112: 379–383. PubMed ID: 12376940
  • Human Gene Mutation Database (Bio-base).
  • Kalay E, Yigit G, Aslan Y, Brown KE, Pohl E, Bicknell LS, Kayserili H, Li Y, Tüysüz B, Nürnberg G, Kiess W, Koegl M, et al. 2011. CEP152 is a genome maintenance protein disrupted in Seckel syndrome. Nature Genetics 43: 23–26. PubMed ID: 21131973
  • Mokrani-Benhelli H, Gaillard L, Biasutto P, Guen T Le, Touzot F, Vasquez N, Komatsu J, Conseiller E, Pïcard C, Gluckman E, Francannet C, Fischer A, et al. 2013. Primary Microcephaly, Impaired DNA Replication, and Genomic Instability Caused by Compound Heterozygous ATR Mutations. Human Mutation 34: 374–384. PubMed ID: 23111928
  • O’Driscoll M, Ruiz-Perez VL, Woods CG, Jeggo PA, Goodship JA. 2003. A splicing mutation affecting expression of ataxia–telangiectasia and Rad3–related protein (ATR) results in Seckel syndrome. Nature Genetics 33: 497–501. PubMed ID: 12640452
  • Tanaka A, Weinel S, Nagy N, O’Driscoll M, Lai-Cheong JE, Kulp-Shorten CL, Knable A, Carpenter G, Fisher SA, Hiragun M, Yanase Y, Hide M, et al. 2012. Germline Mutation in ATR in Autosomal- Dominant Oropharyngeal Cancer Syndrome. The American Journal of Human Genetics 90: 511–517. PubMed ID: 22341969
  • Verloes A, Drunat S, Gressens P, Passemard S. 1993. Primary Autosomal Recessive Microcephalies and Seckel Syndrome Spectrum Disorders. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle,. PubMed ID: 20301772

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.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

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