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Test ID: MECPZ MECP2 Gene, Full Gene Analysis

Useful For

Diagnosis of Rett syndrome or other MECP2-related disorders

Method Name

Polymerase Chain Reaction (PCR) Followed by DNA Sequence Analysis and Gene Dosage Analysis by Multiplex Ligation-Dependent Probe Amplification (MLPA)

Reporting Name

MECP2 Gene, Full Gene Analysis

Specimen Type

Varies


Specimen Required


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.

Additional Information: Specimen preferred to arrive within 96 hours of draw.


Specimen Minimum Volume

1 mL

Specimen Stability Information

Specimen Type Temperature Time
Varies Ambient (preferred)
  Frozen 
  Refrigerated 

Clinical Information

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 in 8,500 to 1 in 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 whom 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 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 nongene-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

An interpretive report will be provided.

Interpretation

All detected alterations are evaluated according to American College of Medical Genetics recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Clinical Reference

1. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015 May;17(5):405-424

2. Moretti P, Zoghbi HY: MeCP2 dysfunction in Rett syndrome and related disorders. Curr Opin Genet Dev 2006;6(3):276-281.

3. Shahbazian MD, Zoghbi HY: Molecular genetics of Rett syndrome and clinical spectrum of MECP2 mutations. Curr Opin Genet Dev 2001;14:171-176.

4. 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.

5. Hagberg B, Hanefeld F, Percy A, Skjedal O: An update on clinically applicable diagnostic criteria in Rett syndrome. Comments to Rett Syndrome Clinical Criteria Consensus Panel Satellite to European Paediatric Neurology Society Meeting, Baden Baden, Germany, 11 September 2001 Eur J Paediatr Neurol 2002:6:293-297

6. Laurvick CL, de Klerk N, Bower C, et al: Rett syndrome in Australia: a review of the epidemiology. J Pediatr 2006:148:347-352

Day(s) and Time(s) Performed

Performed weekly, varies

Analytic Time

14 days

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

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

Test ID Test Order Name Order LOINC Value
MECPZ MECP2 Gene, Full Gene Analysis 35137-9

 

Result ID Test Result Name Result LOINC Value
53512 Result Summary 50397-9
53513 Result In Process
53514 Interpretation In Process
53515 Additional Information 48767-8
53516 Specimen In Process
53517 Source 31208-2
53518 Released By No LOINC Needed

Forms

1. Molecular Genetics: Congenital Inherited Diseases Patient Information (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 (T576) is available in Special Instructions.

3. If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen (http://www.mayomedicallaboratories.com/it-mmfiles/neurology-request-form.pdf)

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

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