Rett Syndrome: MECP2 Sequencing

Clinical Information

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 variant, nonsense variant 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.

Technical Information

• This test is performed by Sanger sequencing.
• Genomic DNA is used to amplify exons 1-4 of the MECP2 gene by standard polymerase chain reaction. Each amplified product is sequenced using the Sanger dideoxy method.

Specimen Requirements

• The preferred sample type is 3-4 ml of peripheral blood collected in an EDTA (purple top) tube. Dried blood spots, extracted DNA, and saliva are also accepted for this test. Blood and saliva kits are available by request.
• Approximately 75 µL of blood should be applied to each of the five circles on a filter paper dried blood spot card. Allow blood to dry for at least 4 hours before shipping.
• Send approximately 5 µg of extracted DNA at a requested concentration of 90-130 ng/µl.
• Saliva samples must be submitted in an approved saliva kit.

Transport Instructions

• The blood specimen should be kept at room temperature and delivered via overnight shipping. 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.
• DBS cards should be shipped at room temperature.
• Extracted DNA should be sent at room temperature via overnight delivery.
•  Saliva is stable at room temperature and can be delivered via overnight or ground shipping.