Nijmegen Breakage Syndrome via the NBN 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
4837 NBN 81479 81479,81479 $540 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4837NBN81479 81479 $540 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.

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

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disease that causes microcephaly, short stature, immunodeficiency, and predisposition to cancer. Approximately half of individuals with NBS develop non-Hodgkin lymphoma or leukemia. Other cancers observed include medulloblastomas, gliomas, and rhabdomyosarcomas. Individuals with NBS are 50 times more likely to develop cancer than people without this condition. Intellectual development is normal in 40% of patients, borderline-to-mild retardation is found in 50% of patients, and 10% of patients are moderately retarded (Kondratenko et al. Adv Exp Med Biol 601:61-7, 2007). Women with NBS often have premature ovarian insufficiency and are infertile. It is estimated that the incidence of NBS is 1 in 100,000, with a higher prevalence in specific European ancestries (i.e. Slavic populations) (Concannon and Gatti. GeneReviews. 2011).

Genetics

Nijmegen breakage syndrome is caused by variants in the NBN gene. The protein product of NBN, Nibrin, normally associates with the MRE11A and RAD50 proteins to form the MRN complex. The MRN complex, upon DNA damage, is involved in DNA repair and cell cycle arrest via the ATM kinase; pathogenic variants in NBN lead to faulty DNA repair and improper cell cycle control. NBS is inherited in an autosomal recessive manner, although carriers of NBN variants may be at a higher risk of malignancies (Ciara et al. Acta Neuropathol 119(3):325-34, 2010; Steffen et al. Int J Cancer 111(1):67-71, 2004). Most variants reported to date in NBN result in truncation variants of Nibrin. The c.657_661del5 variant is the most common variant found in Eastern Europeans with NBS, accounting for more than 90% of all mutant alleles in NBN. Other variants are private and occur in one or a small number of families (Concannon and Gatti. GeneReviews. 2011).

Clinical Sensitivity - Sequencing with CNV PG-Select

Analytical sensitivity should be high because the majority of variants reported are readily detectable by gene sequencing. Most of the variants reported are based on individuals who are homozygous for the single most common Eastern European variant, c.657_661del5, which can be readily detected using sequencing. In the United States, approximately 70% of individuals with NBS tested to date are homozygous for the common allele (c.657_661del5), 15% are heterozygous for c.657_661del5 and a second unique variant, and 15% are homozygous for a unique variant (Concannon and Gatti. GeneReviews. 2011). Individuals homozygous for the NBN c.1089C>A variant have features of Fanconi anemia (Gennery et al. Clin Immunol 113(2):214-9, 2004).

Testing Strategy

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

Indications for Test

Individuals suspected of having Nijmegen breakage syndrome or individuals with a family history, who desire their carrier status. Carrier testing may be important as individuals who have a heterozygous variant in NBN may be at a higher risk for cancer (Ciara et al. Acta Neuropathol 119(3):325-34, 2010; Steffen et al. Int J Cancer 111(1):67-71, 2004). Individuals who show clinical symptoms and who show cellular chromosomal instability (i.e. translocations and inversions involving chromosomes 7 and 14) and/or cellular radiosensitivity. This test is specifically designed for heritable germline variants and is not appropriate for the detection of somatic variants in tumor tissue.

Gene

Official Gene Symbol OMIM ID
NBN 602667
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Nijmegen Breakage Syndrome AR 251260

Related Test

Name
Hyper IgM Syndrome Panel

Citations

  • Ciara et al. (2010). "Heterozygous germ-line mutations in the NBN gene predispose to medulloblastoma in pediatric patients." Acta Neuropathol 119(3):325-34. PubMed ID: 19908051
  • Concannon and Gatti. (2011). "Nijmegen Breakage Syndrome." GeneReviews. PubMed ID: 20301355
  • Gennery et al. (2004). "The clinical and biological overlap between Nijmegen Breakage Syndrome and Fanconi anemia." Clin Immunol 113(2):214-9. PubMed ID: 15451479
  • Kondratenko et al. (2007). "Nijmegen breakage syndrome." Adv Exp Med Biol 601:61-7. PubMed ID: 17712992
  • Steffen et al. (2004). "Increased cancer risk of heterozygotes with NBS1 germline mutations in Poland." Int J Cancer 111(1):67-71. PubMed ID: 15185344

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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