Test ID: FBP1
15q Deletion, Type I and Type II Characterization, Prader-Willi/Angelman Syndromes, FISH
Secondary ID 
A test code used for billing and in test definitions created prior to November 2011
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Useful For Suggests clinical disorders or settings where the test may be helpful
Differentiating between type I and type II deletions in Prader-Willi syndrome and Angelman syndrome patients, as follow-up testing after a SNRPN or D15S10 deletion has been detected by FISH analysis or in patients with a +dic(15) chromosome lacking the SNRPN or D15S10 loci (see DUP15/89365 15q11.2 Duplication, FISH)
Mapping duplications in patients who carry a +dic(15) marker chromosome
Genetics Test Information Provides information that may help with selection of the correct test or proper submission of the test request
Only appropriate to better define the extent of a 15q11.2 deletion originally detected by PWDNA/81153 Prader-Willi/Angelman Syndrome, Molecular Analysis.
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
See Prader-Willi and Angelman Syndromes: Laboratory Approach to Diagnosis in Special Instructions.
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Method Name A short description of the method used to perform the test
Fluorescence In Situ Hybridization (FISH)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Aliases Lists additional common names for a test, as an aid in searching
Angelman syndrome by FISH
del(15)
Prader-Willi syndrome
Prader-Willi syndrome by FISH
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
This test can only be performed if a known SNRPN or D15S10 deletion has been previously identified by FISH analysis or in patients with a dic(15) chromosome.
Provide a reason for referral with each specimen. The laboratory will not reject testing if this information is not provided, but appropriate testing and interpretation may be compromised or delayed.
Forms:
1. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (Supply T576) is available in Special Instructions.
2. If not ordering electronically, submit a Cytogenetics/AFP Congenital Disorders Request Form (Supply T238) with the specimen.
Advise Express Mail or equivalent if not on courier service.
Submit only 1 of the following specimens:
Specimen Type: Amniotic fluid
Container/Tube: Amniotic fluid container
Specimen Volume: 20-25 mL
Collection Instructions:
1. Optimal timing for specimen collection is during 14 to 18 weeks of gestation, but specimens collected at other weeks of gestation are also accepted. Provide gestational age at the time of amniocentesis.
2. Discard the first 2 mL of amniotic fluid.
Additional Information:
1. Place the tubes in a Styrofoam container (Supply T329).
2. Fill remaining space with packing material.
3. Unavoidably, about 1% to 2% of mailed-in specimens are not viable.
4. Bloody specimens are undesirable.
5. If the specimen does not grow in culture, you will be notified within 7 days of receipt.
6. Results will be reported and also telephoned or faxed, if requested.
Specimen Type: Autopsy
Container/Tube: Sterile container with sterile Hank's balanced salt solution (Supply T132), Ringer's solution, or normal saline
Specimen Volume: 4 mm diameter
Collection Instructions:
1. Wash biopsy site with an antiseptic soap.
2. Thoroughly rinse area with sterile water.
3. Do not use alcohol or iodine preparations.
4. Biopsy specimens are best taken by punch biopsy to include full thickness of dermis.
Specimen Type: Blood
Container/Tube: Green top (sodium heparin)
Specimen Volume: 5 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Other anticoagulants are not recommended and are harmful to the viability of the cells.
Specimen Type: Chorionic villi
Container/Tube: 15-mL tube containing 15 mL of transport media
Specimen Volume: 20-25 mg
Collection Instructions:
1. Collect specimen by the transabdominal or transcervical method.
2. Transfer chorionic villi to a Petri dish containing transport medium (Supply T095).
3. Using a stereomicroscope and sterile forceps, assess the quality and quantity of the villi and remove any blood clots and maternal decidua.
Specimen Type: Fixed cell pellet
Container/Tube: Sterile container with a 3:1 fixative (methanol:glacial acetic acid)
Specimen Volume: Entire specimen
Specimen Type: Products of conception or stillbirth
Container/Tube: Sterile container with sterile Hank's balanced salt solution (Supply T132), Ringer's solution, or normal saline
Specimen Volume: 1 cm(3) of placenta (including 20-mg of chorionic villi) and a 1-cm(3) biopsy specimen of muscle/fascia from the thigh
Collection Instructions: If a fetus cannot be specifically identified, collect villus material or tissue that appears to be of fetal origin.
Additional Information: Do not send entire fetus.
Forms: Final Disposition of Fetal/Stillborn Remains (if fetal specimen is sent) in Special Instructions
Specimen Type: Skin biopsy
Container/Tube: Sterile container with sterile Hank's balanced salt solution (Supply T132), Ringer's solution, or normal saline
Specimen Volume: 4 mm diameter
Collection Instructions:
1. Wash biopsy site with an antiseptic soap.
2. Thoroughly rinse area with sterile water.
3. Do not use alcohol or iodine preparations.
4. A local anesthetic may be used.
5. Biopsy specimens are best taken by punch biopsy to include full thickness of dermis.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | NA |
| Lipemia | NA |
| Icterus | NA |
| Other | Clotted blood |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Varies | Ambient (preferred) | |
| Refrigerated | ||
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Prader-Willi (PWS) and Angelman (AS) syndromes are 2 distinct syndromes that can result from either a paternal or maternal deletion of 15q11-q13, respectively. Other mechanisms of inheritance include maternal uniparental disomy (UPD) in PWS, paternal UPD in AS, or abnormal methylation and gene expression.
Both type I and type II 15q11-q13 deletions have been described. Type 1 deletions are larger deletions, spanning breakpoint (BP)1 and distal BP3 breakpoints, while type II deletions are smaller (approximately 500kb), spanning BP2 and BP3. Depending on the deletion type, behavioral differences have been reported in both PWS and AS patients. Type I patients have more severe phenotypes including delayed development and autistic features. Distinguishing between type I and type II deletions is useful in counseling PWS or AS patients. Type I and II deletions may be detected by evaluating the RP11-289D12 region on chromosome 15 with specific DNA probes.
A +dic(15) marker chromosome (an extra or supernumerary dicentric chromosome 15) is often familial and is usually consistent with a normal phenotype, but depending on its size, the marker can be associated with PWS or AS. Larger dic(15) are usually new mutations and are associated with mental retardation and mild dysmorphic features.
See Prader-Willi and Angelman Syndromes: Laboratory Approach to Diagnosis in Special Instructions for additional information.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Interpretation Provides information to assist in interpretation of the test results
Any individual with a normal signal pattern (2 signals) in each metaphase is considered negative for a deletion in the region tested by this probe (see Cautions).
Any patient with a FISH signal pattern indicating loss of the critical region will be reported as having a deletion of the region tested by this probe.
This test should be performed as a reflex test when a SNRPN or D15S10 deletion has been detected by FISH analysis or in patients with a dic(15) chromosome lacking the SNRPN or D15S10 loci.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Because this FISH test is not approved by the FDA, it is important to confirm Prader-Willi syndrome (PWS) or Angelman syndrome (AS) diagnoses by other established methods, such as medical history and clinical evaluation.
This test does not detect uniparental disomy or other methylation abnormalities that cause the PWS or AS phenotype.
Supportive Data
Testing was performed on a series of 35 patients exhibiting a FISH deletion of SNRPN or D15S10, the critical regions on chromosome 15 that are associated with Prader-Willi syndrome (PWS) and Angelman syndrome (AS), respectively. Six of 20 (30%) PWS and 4 of 10 (40%) AS cases exhibited a type I deletion (deletion of RP11-289D12 locus), as did 4 of 5 (80%) referred patients with an unspecified diagnosis. Ten patients with a supernumerary dic(15) were tested with probes for SNRPN, D15S10, and RP11-289D12; in 7 cases both regions were present on both arms of the dic(15), in 2 cases both regions were absent from the dup(15), and 1 case exhibited BP1-BP2 but not SNRPN on both arms of the dic(15). No deletions of RP11-289D12 were detected in 20 specimens with a normal karyotype and no features of either PWS or AS.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Butler MG, Bittel DC, Kibiryeva N, et al: Behavioral differences among subjects with Prader-Willi syndrome and type I and type II deletion and maternal disomy. Pediatrics 2004 Mar;113(3 pt 1):565-573
2. Varela MC, Kok F, Setian N, et al: Impact of molecular mechanisms, including deletion size, on Prader-Willi syndrome phenotype: study of 75 patients. Clin Genet 2005 Jan;67(1):45-52
3. Chai JH, Locke DP, Greally JM, et al: Identification of four highly conserved genes between breakpoint hotspots BP1 and BP2 of the Prader-Willi/Angelman syndromes deletion region that have undergone evolutionary transposition mediated by flanking duplicons. Am J Hum Genet 2003 Oct;73(4):898-925
Method Description Describes how the test is performed and provides a method-specific reference
The detection of deletions associated with type I PWS or AS is based on FISH analysis of the 289D12 and SNRPN region on chromosome 15. Ten metaphase cells from peripheral blood cultures are examined for the presence or absence of the 289D12 locus and SNRPN region along with a 15qter control probe signal. Type 1 deletion are reported when deletion of 289D12 and SNRPN are detected on the same chromosome 15 homolog. Type II deletions are interpreted when deletion of 289D12 but not SNRPN is observed on the same chromosome 15 homolog. (Butler MG, Bittel DC, Kibiryeva N, et al: Behavioral differences among subjects with Prader-Willi syndrome and type 1 or type 2 deletion and maternal disomy. Pediatrics 2004 Mar;113:565-573; Wong KK, deLeeuw RJ, Dosanjh NS, et al: A comprehensive analysis of common copy-number variations in the human genome. Am J Hum Genet 2007 Jan;80[1]:91-104)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Samples processed Monday through Sunday. Results reported Monday through Friday, 8 a.m.-5 p.m. CST.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
88271 x 2-DNA probe, each
88273-Chromosomal in situ hybridization
88291-Interpretation and report
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
| Result ID | Reporting Name | LOINC Code |
|---|---|---|
| 23356 | Specimen | 31208-2 |
| 23357 | Specimen ID | N/A |
| CG039 | Source | N/A |
| 23359 | Order Date | N/A |
| CG041 | Reason For Referral | 42349-1 |
| 23361 | Method | In Process |
| 23362 | Result | In Process |
| 23368 | Interpretation | 69965-2 |
| 23369 | Amendment | In Process |
| 23370 | Consultant | N/A |
| 23371 | Released Date | N/A |
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