MECP2 Sequencing, Family-targeted (Single Exon Sequencing−Known Mutation)

Whole blood, amniotic fluid, chorionic villus sample (CVS) (submission of maternal blood is required for fetal testing) or Labcorp buccal swab kit (buccal swab collection kit contains instructions for use of a buccal swab)

7 mL whole blood, Labcorp buccal swab kit, 10 mL amniotic fluid, or 20 mg CVS

3 mL whole blood, two buccal swabs, 5 mL amniotic fluid, or 10 mg CVS

Lavender-top (EDTA) tube, yellow-top (ACD) tube, sterile plastic conical tube or two confluent T25 flasks for fetal testing, or Labcorp buccal swab kit

Detects mutations in the gene for methyl-CpG-binding protein 2 (MECP2), which causes Rett syndrome, a severe neurological disorder leading to regression of developmental behaviors and expressive language skills.

This test does not detect variants in any other gene, nor does it detect genomic deletions or promoter or deep-intron variants. Molecular-based testing is highly accurate, but as in any laboratory test, rare diagnostic errors may occur.

DNA sequencing

There are some suspected cases in males, but Rett syndrome primarily affects females. It is the second most common cause of intellectual disability in females (frequency: 1:15,000 to 1:8,500 births). The risk of development of Rett syndrome seems to be equal among different ethnic groups.

Mutations in the gene for methyl-CpG-binding protein 2 (MECP2) are the most common cause of Rett syndrome. The MECP2 protein is one of the many components involved with the regulation of gene expression. Rett syndrome is considered to be the first syndrome identified directly related to mutations in a gene controlling gene expression.

The MECP2 gene is located on the X chromosome. Currently, the criterion for Rett syndrome diagnosis is completely clinical. A group of standardized clinical benchmarks has been used to identify Rett syndrome and to distinguish relative subsets within the Rett population. The most clinically-defined group is referred to as classic Rett. Of these, the majority (80%) have MECP2 gene mutations. Although 12 mutations account for 73% of mutation-positive cases, nearly 300 disease-causing mutations have been identified.