Rett syndrome (MECP2) Sequencing and MLPA
|Clinical info||A neurodevelopmental disorder that affects females, Rett syndrome is associated with cortical atrophy, stereotypical hand movements and severe intellectual disability. With an incidence of 1 in 10,000 - 15,000, it is one of the most common causes of intellectual disability in females. Rett syndrome is characterized by loss of acquired skills after a period of normal development in infancy. Most cases of Rett syndrome are caused by an abnormality (missense mutation, nonsense mutation or deletion) of MECP2.
Additionally, a specific phenotype has been identified in males with a MECP2 duplication that is identifiable by MLPA. These males display hypotonia that progresses to spasticity, severe intellectual disability and recurrent pulmonary infections. Females in these families who have the duplication are clinically unaffected and display a near total skewing of X-inactivation.
Sequencing of the MECP2 gene and MLPA deletion/duplication analysis can be ordered concurrently, sequentially or separately.
|Indications||Molecular testing is useful to confirm the diagnosis and to identify the disease causing mutation within a family to allow for carrier testing and prenatal diagnosis.|
|Associated Tests||CDKL5 (STK9) atypical Rett syndrome sequencing, FOXG1 Congenital Rett syndrome variant sequencing, Rett/Angelman 2nd tier panel, X-Inactivation studies|
|Detection||Sequencing of the MECP2 gene will detect mutations in approximately 80% of individuals with Rett syndrome. Of those with a normal sequencing result, approximately 15% will have a deletion or duplication identified by MLPA.|
|Specimen Requirements||5 to 10 ml of peripheral blood collected in an EDTA (lavender top) Vacutainer tube is preferred. The minimal blood needed for reliable DNA isolation is 3 ml|
|Transport||The specimen should be kept at room temperature and delivered via overnight shipping. FedEx is preferred. If shipment is delayed by one or two days, the specimen should be refrigerated and shipped at room temperature. Do not freeze the specimen. Samples collected on Friday can be safely designated for Monday delivery.|
|Turnaround time||Sequencing: 3 weeks
Deletion/Duplication: 3 weeks
|CPT Codes||Sequencing - unknown mutation
MLPA analysis for deletion/duplication analysis
|Prenatal testing||Prenatal diagnosis is available if the familial mutation is known. Additional fees for cell culture and maternal cell contamination may apply. Maternal cell contamination studies are required for all prenatal molecular tests. Contact the laboratory prior to sending a prenatal specimen.|
|Cost||$900 for sequencing
$350 for known mutation
$500 for MLPA analysis
Molecular Diagnostic Lab
The Molecular Diagnostic Lab offers DNA analysis for many genetic disorders via gene sequencing, targeted mutation analysis, MLPA deletion/duplication testing, trinucleotide repeat analysis and next generation sequencing panels.