Test name: Rett/Atypical Rett/Angelman Panel - Next Generation Sequencing
Disorders Included in This Panel:
- Classic Rett (MECP-Related Disorders) GeneReviews™
- Atypical Rett
- Angelman GeneReviews™
- Pitt-Hopkins GeneReviews™
- X-linked mental retardation, Christianson type
- Developmental delay, with or without regression
- Mild to severe intellectual disability
- Lack of speech/apraxia
- Low muscle tone
- Ataxic gait
- Dysmorphic or normal facial features
- Concerning stereotypic behaviors such as hand-wringing, hand-flapping, inappropriate laughter
The genes on this panel are included on another NGS panel offered by our laboratory:
For assistance determining which Next Gen panel is most useful for your patient, please call our laboratory at 402-559-5070 and ask to speak with a laboratory genetic counselor.
GENE LIST 2
- GeneList2 (8/15/2013 - current)
Panel expanded to include 2 additional genes (CNTNAP2 and NRXN1) associated with Rett, Atypical Rett, and/or Angelman syndromes.
- GeneList1 (10/1/2012 - 8/14/2013)
- Next generation sequencing (NGS), or “Next Gen” as it is frequently called, is a technology that analyzes multiple genes at once. It is a cost-effective method of testing many potentially causative genes simultaneously rather than ordering separate Sanger sequencing one gene at a time.
- Next Gen is most helpful in cases where a patient has findings suspicious of multiple potential genetic causes, generally the result of either clinical ambiguity due to marked phenotypic overlap between various syndromes or numerous genetic causes for a single disorder.
- Our systematic data analysis references the most current versions of primary genomic databases, which translates to better mutation classification (e.g., benign vs. pathogenic).
- Pathogenic changes are confirmed by traditional Sanger sequencing or by another appropriate testing method.
- Even after careful analysis, some variants cannot yet be classified as benign or pathogenic and, therefore, are variants of uncertain significance.
- Next Gen will identify sequence variation, but it will not identify large deletions or duplications. A complimentary test such as whole genome microarray analysis or gene-specific deletion/duplication analysis would be needed to identify genetic dosage abnormalities.
- Next Gen is NOT whole exome sequencing or whole genome sequencing. The test will only identify mutations in the genes included on the panel ordered.
- Approximately 8% of individuals with classic Rett syndrome and 3% of those with atypical Rett syndrome are found to have partial or whole gene deletions or duplications of MECP2 which are not identifiable by sequencing*. MECP2 deletion and duplication analysis is available by Multiple Ligation Probe Analysis (MLPA).
- Approximately 78% of individuals with Angelman syndrome are found to have methylation abnormalities of Chromosome 15 identified through Methylation Analysis.*
- Phenotypic features of Rett syndrome, atypical Rett syndrome, and Angelman syndrome overlap with the features of multiple microdeletion and microduplication syndromes. High Density SNP Microarray can be ordered simultaneously or in a tiered fashion to assess for these copy number changes. NOTE: High Density SNP Microarray is not a substitution for MLPA analysis of MECP2.
- Similarly, due to the phenotypic overlap between various syndromes, the NGS Autism/ID/MA Panel, which covers all the genes in the Rett/Atypical Rett/Angelman Syndromes Next Gen Panel, as well as additional genes of clinical significance, may be appropriate for some patients.
*Reference Source: GeneReviews™
For questions regarding the usefulness of complementary testing for your patient, please call our laboratory at 402-559-5070 and ask to speak with a laboratory genetic counselor.
Specimen requirements: Test kits are available – please contact the laboratory
- Blood: One 3-5 ml EDTA (purple top) tube
- Expanded Panel: For patients who have not previously been tested on GeneList1
- 81302, and 81404 (x2)
- Expanded Panel: For patients who have previously been tested on GeneList1
Please contact the laboratory for questions regarding GeneList1 billing.
Pricing: Contact the laboratory billing staff for current costs
Required forms: Postnatal Test Request Form
Turn-around time: 6-10 weeks
Step-by-step ordering instructions:
1) Access the postnatal test request form on the Human Genetics Laboratory website.
2) Complete the 2-page form. Under TEST SELECTION, mark the box next to the Next Generation Sequencing Rett/Atypical Rett/RASopathy Disorders Panel.
3) When ordering multiple tests, such as the High Density SNP Microarray: Under SPECIAL TEST INSTRUCTIONS, indicate the order in which you would like the tests performed. For example, “Please complete microarray first. If negative, reflex to Next Gen Sequencing.”
4) Provide any clinical information that may be important for interpretation.
5) Obtain insurance pre-authorization when necessary; forms available.
6) Following HGL shipping & handling requirements, send completed test request form and specimen at room temperature within 24 hours of collection.