Mutations in Only One MeCP2 Protein Form Leads to Milder Rett Symptoms in Boy, Report Indicates

Mutations that affect a specific form of the MeCP2 protein may lead to milder symptoms of Rett syndrome in males, the case report of a 9-year-old boy suggests.

The study, “MeCP2_e2 partially compensates for lack of MeCP2_e1: A male case of Rett syndrome,” was published in the journal Molecular Genetics & Molecular Medicine.

Rett syndrome is almost always caused by mutations in the MECP2 gene. That gene gives instructions for making the MeCP2 protein, which plays important roles in nerve cell function and communication.

As MECP2 is located on the X chromosome, the disorder affects mostly girls.  However, because males have only one X chromosome, an alteration in MECP2 is not compensated by production of normal protein in the other chromosome. That is why the disease was recognized initially only in females and thought to be lethal in males.

Yet, here have been reports of males with Rett syndrome. Typically, these patients have more severe symptoms that develop earlier, beginning at birth or shortly after.

A few specific biological processes can explain why some males with Rett survive. One is mosaicism, which refers to the presence of different groups of cells in the body that are genetically distinct.

In the case of males with Rett, this means that the MECP2 gene is altered in some cells, while in others the gene copy is normal. This happens when a mutation appears during embryonic development. As each cell gives rise to many more cells, the earlier the mutation occurs during development means more cells will have the alteration.

The severity of the disease depends on the percentage of affected cells — the more cells with mutated MECP2 gene the more severe the symptoms.