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Spectrum: Autism Research News

Reference strains aid genetic testing for Rett syndrome

by  /  26 March 2014

This article is more than five years old. Autism research — and science in general — is constantly evolving, so older articles may contain information or theories that have been reevaluated since their original publication date.

Genetic testing: Tests for Rett syndrome need to detect the hundreds of different mutations seen in MeCP2 in people with the syndrome.

Researchers have established a set of commercially available cell lines that can help gauge the quality of tests for Rett syndrome, they reported in the March issue of the Journal of Molecular Diagnostics1

Rett syndrome is an autism-related disorder characterized by a sudden loss of language and motor skills around 1 year of age. In most cases, it is caused by mutations in the MeCP2 gene. Despite this clear genetic cause, there is no federally approved genetic test for Rett. Each clinical laboratory uses its own homegrown assay.

Any comprehensive Rett test must be able to detect the myriad MeCP2 mutations found in people with the syndrome. About 60 percent of Rett cases can be traced back to eight mutations that each change a single DNA base in the gene. Overall, however, there are hundreds of MeCP2 mutations that can cause Rett.

To test the reliability of a genetic test for Rett, laboratories need reference strains with known MeCP2 mutations. Few of these strains have been commercially available, so the researchers generated 34 reference cell lines, available from the NIGMS Human Genetic Cell Repository.

The researchers started with eight existing Rett syndrome cell lines from the Coriell Cell Repositories. They also took blood samples from 27 individuals with Rett syndrome and derived immortal cell lines from them.

The 34 cell lines include the eight common mutations, as well as duplications and deletions within the gene, mutations that shift the genetic code and ones that alter correct splicing of the gene into protein.

The researchers sent these cell lines to up to five laboratories that perform routine clinical genetic testing. Each of the laboratories identified and confirmed the syndrome-causing mutation in each of the cell lines. 

Mutations in MeCP2 are generally lethal in boys, making Rett syndrome a mainly female disorder. The collection includes two rare mutations from males with Rett.


1: Kalman L.V. et al. J. Mol. Diagn. 16, 273-279 (2014) PubMed