New Rett-causing Mutation Found in 4-year-old, Despite Testing Glitch

Marisa Wexler MS avatar

by Marisa Wexler MS |

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A newly found mutation in the MECP2 gene that causes Rett syndrome was described in a recent report.

The report highlights some of the considerations that need to be taken into account when testing for an unknown Rett-causing mutation. Here, a testing glitch showed an artificial result from the blood sample of a 4-year-old girl in China.

“Each molecular diagnostic technique has its drawbacks,” the researchers wrote.

The team noted that reporting the new mutation “can help in the genetic counseling and prenatal diagnosis of disorders of MECP2 defects.”

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The study, “Case Report: Prenatal Diagnosis for a Rett Syndrome Family Caused by a Novel MECP2 Deletion With Heteroduplexes of PCR Product,” was published in the journal Frontiers in Pediatrics.

The case centered on a Chinese girl, from Zhejiang province, who had been diagnosed with Rett syndrome. In the first year of the child’s life, her development was normal, and she had started to talk. However, by age 13 months, she was no longer speaking, and shortly thereafter, she no longer responded to her parents’ call by turning her head. She also lost motor skills and started performing repetitive hand movements. At 30 months of age, she started to experience seizures.

The girl’s mother had become pregnant, and requested prenatal genetic testing of the unborn fetus.

“To perform the prenatal diagnosis, we first had to know the genetic basis of Rett syndrome” in the 4-year-old girl, the researchers wrote.

The team collected blood samples from the girl, and extracted DNA for analysis. Those analyses focused on the MECP2 gene, mutations of which account for most cases of Rett syndrome.

Results revealed a deletion in the MECP2 gene. This disease-causing mutation, heterozygous — found in only one gene copy — and not described before, was dubbed c.441_1153del713 based on the specific region affected.

“We reported a novel MECP2 heterozygous deletion in a Rett syndrome family,” the team concluded.

Over the course of DNA analysis, the researchers did a standard test that involves running DNA through a gel with an electric current. This separates the DNA into “bands” based on size, which can be useful for detecting large mutations like deletions — the mutated gene will be smaller than the healthy gene because of the deletion, so it will form a separate band.

When the researchers did this test on the patient’s DNA, results revealed three bands — one representing the healthy gene and a second band with the deletion.

Theoretically, it is possible that a third band like this could indicate mosaicism, which occurs when different cells in the body have different genetic makeup. However, further analyses revealed that the third band was actually an artificial result of the lab tests made of pieces of both mutated and healthy DNA, and so appeared to be a different size.

This experience “provided a reference for the prenatal diagnosis of genetic diseases with complicated mutations, not limited to Rett syndrome,” the team concluded.