MECP2 Deletion/Duplication Analysis

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

7 mL whole blood or 4 buccal swabs; 10 mL amniotic fluid or 10 mg CVS for fetal testing

3 mL whole blood or 2 buccal swabs; 5 mL amniotic fluid, or 10 mg CVS for fetal testing

Lavender top (EDTA) or yellow-top (ACD) or Labcorp buccal swab kit; sterile plastic conical tube or two confluent T-25 flasks for fetal testing

Detects single exon or multiexon deletions and duplication 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.

MLPA is designed to detect single exon, multi-exon, and full gene deletions or duplications. MLPA may not detect certain genomic rearrangements, such as translocations, inversions, mosaic variants, or some partial exon rearrangements. This assay cannot determine exact breakpoints of deletions or duplications detected.

This test was developed and its performance characteristics determined by Labcorp. It has not been cleared or approved by the Food and Drug Administration.

Multiplex ligation-dependent probe amplification (MLPA)

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 methy-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. Exonic and whole gene deletions account for 8% to 10% of MECP2 pathogenic variants.