Test ID: ME2MS
MECP2 Gene, Full Gene Analysis
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
Diagnosis of Rett syndrome or other MECP2-related disorders
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
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
Polymerase Chain Reaction (PCR) Followed by DNA Sequence Analysis and Gene Dosage Analysis by Multiplex Ligation-Dependent Probe Amplification (MLPA)
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)
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
MECP2 Duplication Syndrome
Methyl-CpG-Binding Protein 2
Rett Syndrome
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.
Specimen must arrive within 96 hours of draw.
Specimen Type: Whole blood
Container/Tube:
Preferred: Lavender top (EDTA) or yellow top (ACD)
Acceptable: Any anticoagulant
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send specimen in original tube.
Forms:
1. Molecular Genetics-Congenital Inherited Diseases Patient Information Sheet (Supply T521) in Special Instructions
2. 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.
3. If not ordering electronically, submit a Molecular Genetics Request Form (Supply T245) with the specimen.
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
No specimen should be rejected. If specimen not received at appropriate temperature or in wrong anticoagulant, include note to laboratory. If questions, contact laboratory.
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) | |
| Frozen | ||
| Refrigerated | ||
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Methyl-CpG-binding protein 2 (MeCP2) is a transcriptional repressor protein encoded by the MECP2 gene located on the X chromosome. Genetic mutations in MECP2 alter the expression of targeted genes and can be associated with variable phenotypes in females including classic Rett syndrome, variant or atypical Rett syndrome, mild mental retardation, and asymptomatic carriers. Males with MECP2 mutations can present with variable phenotypes as well. The variability in males can, in part, be attributed to the type of MECP2 mutation present; point mutations are typically associated with severe neonatal encephalopathy and gene duplications are associated with MECP2 duplication syndrome. Full MECP2 gene analysis via sequencing and large duplication/deletion studies has been useful in identifying germline mutations in individuals with these clinical presentations.
Rett Syndrome
Rett syndrome is an X-linked, panethnic condition with an incidence of approximately 1/8,500 to 1/15,000 females. Disease course typically begins after 6 to 18 months of apparently normal development with rapid regression in language and motor skills. A hallmark feature of this condition is repetitive, stereotyped hand movements, sometimes described as hand-wringing. Clinical criteria have been established for diagnosis of classic and atypical or variant Rett syndrome. Greater than 88% of females with a clinical diagnosis of classic Rett syndrome demonstrate a mutation by this test. The detection rate is approximately 43% for females with a clinical diagnosis of atypical or variant Rett syndrome. For individuals in which there is clinical suspicion for Rett syndrome but clinical criteria are not met, the detection rate is lower given the phenotypic overlap with other conditions (eg, Angelman syndrome).
Nonrandom X chromosome inactivation, resulting in phenotypic variability within families, has been reported in females with MECP2 mutations. Although 99.5% of mutations associated with Rett syndrome are de novo, asymptomatic or very mildly affected carrier mothers of classically affected daughters have been reported. Genetic counseling should be provided with this, and the possibility of germline or somatic mosaicism, in mind.
MECP2 Duplication Syndrome
Although MECP2 mutations are reported in males, these males typically do not present with classic Rett syndrome unless an abnormal karyotype (ie, 47,XXY) or somatic mosaicism is also present. More commonly, MECP2 mutations have been reported in karyotypically normal males presenting with neonatal encephalopathy and mental retardation syndromes. MECP2 duplication syndrome is an increasingly reported severe mental retardation syndrome characterized by infantile hypotonia, absence of speech, and progressive spasticity. Seizures and recurrent respiratory infections are commonly reported as well. These MECP2 gene duplications vary in size from 0.3 Mb to 2.3 Mb. Although chromosome analysis can identify some larger duplications, other methods such as multiplex ligation-dependent probe amplification (MLPA) can identify essentially all MECP2 gene duplications. Males with non-gene duplication type mutations can present with other mental retardation syndromes (ie, Angelman-like syndrome) or neonatal encephalopathy and early death.
To date, all males found to have an MECP2 duplication are clinically affected and have inherited the duplication from their asymptomatic mothers. Therefore, mothers of sons with MECP2 duplication syndrome are thought to be obligate carriers whose male offspring have a 50% risk of being affected.
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
An interpretive report will be provided.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
A small percentage of individuals who are carriers or have a diagnosis of a MECP2-related disorder may have a mutation that is not identified by this method (eg, promoter mutations, deep intronic alterations). The absence of a mutation(s), therefore, does not eliminate the possibility of positive carrier status or the diagnosis of a MECP2-related disorder. For carrier testing, it is important to first document the presence of a MECP2 gene mutation in an affected family member.
In some cases, DNA alterations of undetermined significance may be identified.
Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.
A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given to us is inaccurate or incomplete.
In addition to disease-related probes, the MLPA technique utilizes probes localized to other chromosomal regions as internal controls. In certain circumstances, these control probes may detect other diseases or conditions for which this test was not specifically intended. Results of the control probes are not normally reported. However, in cases where clinically relevant information is identified, the ordering physician will be informed of the result and provided with recommendations for any appropriate follow-up testing.
Phenotypic overlap exists between MECP2-related conditions and several conditions not associated with MECP2 mutations. This assay will not detect alterations in other genes or chromosomal rearrangements that could result in a similar phenotype.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Moretti P, Zoghbi HY: MeCP2 dysfunction in Rett syndrome and related disorders. Curr Opin Genet Dev 2006;6(3):276-281.
2. Shahbazian MD, Zoghbi HY: Molecular genetics of Rett syndrome and clinical spectrum of MECP2 mutations. Curr Opin Genet Dev 2001;14:171-176.
3. Van Esch H, Bauters M, Ignatius J, et al: Duplication of the MECP2 region is a frequent cause of severe mental retardation and progressive neurological symptoms in males. Am J Hum Genet 2005;77:442-453.
4. Hagberg B, Hanefeld F, Percy A, Skjedal O: An update on clinically applicable diagnostic criteria in Rett syndrome. European Journal of Paediatric Neurology 2002:6:293-297.
5. Laurvick CL, de Klerk N, Bower C, et al: Rett syndrome in Australia: A review of the epidemiology. The Journal of Pediatrics 2006:148:347-352.
Method Description Describes how the test is performed and provides a method-specific reference
Fluorescent DNA sequence analysis is used to test for the presence of mutations in all 4 exons of the MECP2 gene. Additionally, gene dosage analysis (multiplex ligation-dependent probe amplification) is used to test for the presence of large deletions and duplications in this gene. GenBank accession number; NM_004992. (Unpublished Mayo method)
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.
Tuesday; 10 a.m.
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
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.
81302-MECP2 (methyl CpG binding protein 2) (eg, Rett syndrome) gene analysis; full sequence analysis
81304-MECP2 (methyl CpG binding protein 2) (eg, Rett syndrome) gene analysis; duplication/deletion variants
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 |
|---|---|---|
| 50196 | Specimen | 31208-2 |
| 50197 | Specimen ID | N/A |
| 50198 | Source | N/A |
| 50199 | Order Date | N/A |
| 50200 | Reason For Referral | 42349-1 |
| 50201 | Method | In Process |
| 50202 | Result | 35137-9 |
| 50203 | Interpretation | 69047-9 |
| 29390 | Extraction Performed? | N/A |
| 50879 | MLPA Performed? | N/A |
| 50204 | Amendment | In Process |
| 50205 | Reviewed By | N/A |
| 50206 | Release Date | N/A |
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