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Molecular Genetics Laboratory

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Rett Syndrome / MECP2 Related Disorders (MECP2 Sequencing)

  • Synonyms: MECP2 Related Disorders, RTT, MRXS13
  • LIS Mnemonic: MBMECSEQ


    Collect whole blood in a purple top (EDTA) tube (preferred). Extracted DNA is also acceptable.

    Volume Required

    5 ml whole blood or 3 ug extracted DNA

    Minimum Required

    3 ml whole blood


    Refrigerate sample until shipment. Send the sample at room temperature with overnight delivery for receipt Monday through Friday within 24 hours of collection.


    Whole blood can be refrigerated until shipment.

    Unacceptable conditions

    Heparinized specimens, severely hemolyzed specimens, frozen, clotted or possibly commingled specimens, blood in non-sterile or leaky containers, mislabeled or inappropriately labeled specimens.

    Specimen Handling

    Do not heat, freeze or centrifuge blood before shipment. Refrigerate sample until shipment.

Days Performed

Mon - Fri 9:00am to 4:00pm


4-6 weeks



Disease Information

Clinical Features:

MECP2-related disorders include: classic Rett syndrome, atypical Rett syndrome, and very mild learning disabilities in females, and neonatal encephalopathy in males and syndromic or nonsyndromic mental retardation syndromes in males. Rett syndrome is characterized by the progressive loss of intellectual functioning, fine and gross motor skills, communication skills, deceleration of head growth, and the development of stereotypic hand movements, occurring after a period of normal development. While classic Rett syndrome is defined on the basis of strict diagnostic criteria, atypical forms of Rett do exist that vary in terms of age of onset (congenital and late regression variants) as well as symptom severity (preserved speech variant). MECP2 mutations may also be found in males and females exhibiting X-linked mental retardation and in some males and females with Angelman-like phenotype. Males with MECP2 mutations have severe neonatal encephalopathy and generally do not survive beyond the first year of life. The MECP2 duplication syndrome occurs mainly in males and is characterized by infantile hypotonia, severe mental retardation, absence of speech, progressive spasticity, recurrent respiratory infections and seizures. Duplications of the MECP2 gene range from 0.3 to 2.3 Mb and are believed to be completely penetrant in males.

Molecular Genetics:

The MECP2 (Methyl CpG Binding Protein 2) gene is located on Xq28 and contains four exons. MECP2 is a transcriptional repressor protein that is known to possess two critical functional regions, the methyl binding domain (MBD) which binds specifically to DNA at methylated CpG's, and the transcriptional repression domain (TRD) that is responsible for recruiting other proteins that mediate transcription repression. DNA methylation-dependent repression is important for X-chromosome inactivation (XCI) and genomic imprinting. More than 200 pathogenic mutations including missense, nonsense and deletions have been identified throughout the MECP2 gene.

Test Methods:

We offer DNA sequence analysis of the entire coding region. PCR amplification and sequencing is performed on all coding exons including splice junctions. The patient’s gene sequence is then compared to a reference sequence. Sequence variants are classified as mutations, variants of unknown significance or benign variants unrelated to disease. Variants of unknown significance may warrant further studies in the patient and other family members. Mutations in promoters, deep intronic regions and other regulatory regions will not be identified with this assay.

Detection Rate:

Point mutations have been identified in 70-80% of girls with classic Rett syndrome and 20% of girls with a variant diagnosis.

Related Tests:

Atypical Rett syndrome/Infantile Spasms Panel: ARX/MECP2/CDKL5 Sequencing + MECP2 Deletion/Duplication Analysis Atypical Rett syndrome: CDKL5 Gene Sequencing Infantile Spasms: ARX Sequencing Congenital Variant of Rett syndrome: FOXG1 Sequencing Known mutation analysis is available to family members for mutations previously identified by sequence analysis or deletion/duplication analysis. Prenatal Testing is available to adult females who are confirmed carriers of mutations. Please contact the laboratory director to discuss appropriate testing prior to collecting a prenatal specimen.


Test results with interpretation will be mailed and/or faxed to the referring physician or laboratory following completion of the test. Additional reports will be provided as requested.


The clinical utility of such testing is to support a clinical diagnosis of the disease, facilitate genetic counseling, assess the risk to other first degree relatives and to facilitate testing of at - risk family members.

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