Osteogenesis Imperfecta via the FKBP10 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
8309 FKBP10 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8309FKBP1081479 81479(x2) $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.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

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 13 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn 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

  • Juan Dong, PhD, FACMG

Clinical Features and Genetics

Clinical Features

Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous skeletal disorder characterized by frequent bone fractures with or without minimal trauma. Clinical signs of OI can range from mild to severe. In addition to bone fractures, patients may have scoliosis, bowing of long bones, short stature, blue sclera, hearing loss, dentin defects, muscle weakness or joint laxity. The incidence is approximately 6-7/100,000 (Dijk et al. 2012). ~90% of clinically diagnosed OI is caused by mutations in the COL1A1 and COL1A2 genes, while ~10% is caused by mutations in the CRTAP, FKB10, LEPRE1, PLOD2, PPIB, SERPINF1, SERPINH1, SP7, WNT1, IFITM5, BMP1, TMEM38B and other undefined genes (Dijk et al. 2012; Valadares et al. 2014).

Genetics

Mutations in the FKBP10 gene cause a rare severe form of autosomal recessive type XI OI, Bruck syndrome and Kuskokwim syndrome. Bruck syndrome, an osteogenesis imperfecta phenotypic spectrum disorder, is characterized by congenital contractures with pterygia, bone fractures in infancy or early childhood, postnatal short stature, severe limb deformity, and progressive scoliosis. Kuskokwim syndrome is defined by congenital joint contracture with minor bone fractures and occurs solely among populations in Central Alaskan Yupik. The FKBP65 protein coded by the FKBP10 gene belongs to a family of immunophilins and may serve as a peptidylprolyl isomerase required for lysyl hydroxylase activity in forming mature cross-links in bone collagen. To date, ~ 20 unique causative mutations have been identified. They are missense, nonsense, splicing site and small deletions/insertions. No large deletions or duplications have been reported (Shaheen et al. 2010; Barnes et al. 2013; Human Gene Mutation Database). A founder mutation c.948dup (p.Ile317Tyrfs*56) was found in patients from Samoa and nearby islands in the South Pacific (Schwarze (2013). Another founder mutation c.877_879delTAC (p.Tyr293del) was seen in Kuskokwim syndrome. ~ 3% of the population in Central Alaskan Yupik are carriers for this mutation (Barnes et al. 2013).

Clinical Sensitivity - Sequencing with CNV PGxome

Due to limited publications, clinical sensitivity is currently unknown. In one publication, FKBP10 mutations were identified in 21 families affected with either autosomal recessive OI or Bruck syndrome (Schwarze et al. 2013). The mutation detection rate should be high, because all reported FKBP10 mutations are point mutations or small deletions and insertions, which can be detected by sequencing.

Testing Strategy

This test provides full coverage of all coding exons of the FKBP10 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. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Candidates for this test are patients with symptoms consistent with autosomal recessive OI type XI, Bruck syndrome type I and Kuskokwim syndrome, who have no mutations in the COL1A1 and COL1A2 genes and the family members of patients who have known FKBP10 mutations. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in FKBP10.

Gene

Official Gene Symbol OMIM ID
FKBP10 607063
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Osteogenesis Imperfecta, Type XI AR 610968

Citations

  • Barnes AM, Duncan G, Weis M, Paton W, Cabral WA, Mertz EL, Makareeva E, Gambello MJ, Lacbawan FL, Leikin S, Fertala A, Eyre DR, et al. 2013. Kuskokwim Syndrome, a Recessive Congenital Contracture Disorder, Extends the Phenotype of FKBP10  Mutations. Human Mutation 34: 1279-1288. PubMed ID: 23712425
  • Dijk FS Van, Byers PH, Dalgleish R, Malfait F, Maugeri A, Rohrbach M, Symoens S, Sistermans EA, Pals G. 2012. EMQN best practice guidelines for the laboratory diagnosis of osteogenesis imperfecta. European Journal of Human Genetics 20: 11-19. PubMed ID: 21829228
  • Human Gene Mutation Database (Bio-base).
  • Schwarze U, Cundy T, Pyott SM, Christiansen HE, Hegde MR, Bank RA, Pals G, Ankala A, Conneely K, Seaver L, Yandow SM, Raney E, et al. 2013. Mutations in FKBP10, which result in Bruck syndrome and recessive forms of osteogenesis imperfecta, inhibit the hydroxylation of telopeptide lysines in bone collagen. Hum Mol Genet 22: 1-17. PubMed ID: 22949511
  • Shaheen R, Al-Owain M, Faqeih E, Al-Hashmi N, Awaji A, Al-Zayed Z, Alkuraya FS. 2011. Mutations in FKBP10 cause both Bruck syndrome and isolated osteogenesis imperfecta in humans. Am. J. Med. Genet. 155: 1448-1452. PubMed ID: 21567934
  • Valadares ER, Carneiro TB, Santos PM, Oliveira AC, Zabel B. 2014. What is new in genetics and osteogenesis imperfecta classification? Jornal de Pediatria 90:536-41. PubMed ID: 25046257

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.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


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.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: $
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