Collect whole blood in a purple top (EDTA) tube (preferred). Extracted DNA and saliva are also acceptable.
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.
Storage/Transport Temperature
For CHOP Phlebotomy: Samples can be collected throughout the week. Samples collected on weekends or holidays are held in Central Labs and sent to the Genomic Diagnostic Lab the following business day.
For External Clients: Refrigerate sample until shipment. Send the sample at room temperature with overnight delivery for receipt Monday through Friday, optimally within 24 hours of collection.
Please contact the lab (267-426-1447) with questions regarding non-blood specimens.
Volume Required
5 ml whole blood or 3 ug extracted DNA
Minimum Required
3 ml whole blood
Phlebotomy Draw
Yes
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.
Performing Lab
Division of Genomic Diagnostics
Performed
Mon - Fri 9:00am to 4:00pm
Reported
28 days
Detection Rate
Point mutations have been identified in 70-80% of girls with classic Rett syndrome and 20% of girls with a variant diagnosis. MECP2 deletions are found in approximately 20-30% of girls with classic Rett syndrome and 3% of girls with atypical forms of Rett syndrome. Duplication of the MECP2 gene is detected in 17% of the cases with the specific MECP2 duplication phenotype.
Utility
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.
Synonyms
MECP2 Related Disorders, RTT, MRXS13, Rett Syndrome / MECP2 Related Disorders (MECP2 Sequencing and Deletion/Duplication Analysis)
MECFS
LIS Mnemonic
MECFS
Available STAT
No
Test Notes
We offer DNA sequence analysis and deletion/duplication testing of the entire coding region. These tests can be ordered together as a panel or separately. 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.
Large deletions and duplications in the MECP2 gene will be detected using multiplex ligation-dependent probe amplification assay (MLPA).
Molecular Testing Notes
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.
CPT Codes
81302, 81304
Collection
Collect
Collect whole blood in a purple top (EDTA) tube (preferred). Extracted DNA and saliva are also acceptable.
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.
Storage/Transport Temperature
For CHOP Phlebotomy: Samples can be collected throughout the week. Samples collected on weekends or holidays are held in Central Labs and sent to the Genomic Diagnostic Lab the following business day.
For External Clients: Refrigerate sample until shipment. Send the sample at room temperature with overnight delivery for receipt Monday through Friday, optimally within 24 hours of collection.
Please contact the lab (267-426-1447) with questions regarding non-blood specimens.
Volume Required
5 ml whole blood or 3 ug extracted DNA
Minimum Required
3 ml whole blood
Phlebotomy Draw
Yes
Ordering
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.
Performing Lab
Division of Genomic Diagnostics
Performed
Mon - Fri 9:00am to 4:00pm
Reported
28 days
Detection Rate
Point mutations have been identified in 70-80% of girls with classic Rett syndrome and 20% of girls with a variant diagnosis. MECP2 deletions are found in approximately 20-30% of girls with classic Rett syndrome and 3% of girls with atypical forms of Rett syndrome. Duplication of the MECP2 gene is detected in 17% of the cases with the specific MECP2 duplication phenotype.
Utility
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.
Synonyms
MECP2 Related Disorders, RTT, MRXS13, Rett Syndrome / MECP2 Related Disorders (MECP2 Sequencing and Deletion/Duplication Analysis)
MECFS
LIS Mnemonic
MECFS
Available STAT
No
Test Notes
We offer DNA sequence analysis and deletion/duplication testing of the entire coding region. These tests can be ordered together as a panel or separately. 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.
Large deletions and duplications in the MECP2 gene will be detected using multiplex ligation-dependent probe amplification assay (MLPA).
Molecular Testing Notes
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.
