New MeCP2 mutation found in boy with Rett syndrome
Nonsense mutation discovery may aid in early diagnosis
Researchers identified a new mutation in the MeCP2 gene in a Chinese boy diagnosed with Rett syndrome, a condition that rarely affects males.
The boy exhibited diverse symptoms, including limited movements, breathing and sleep problems, heart and lung defects, and abnormal brain wave activity.
“Our discovery of a new spontaneous MeCP2 nonsense mutation enriches the understanding of Rett syndrome and provides a reference for its early diagnosis and treatment,” the researchers wrote.
The study, “Proteomic analysis of serum from a MeCP2 patient reveals an arginine biosynthesis pathway affected by the p.Lys254* variant,” was published in Clinical Case Reports.
Rett syndrome is most commonly caused by mutations in the MeCP2 gene, which provides instructions for making the MeCP2 protein, which helps to control the activity of genes and is particularly important in brain function and development. The MeCP2 gene is located on the X chromosome.
Rett in boys
Rett almost exclusively occurs in girls, who have two X chromosomes. Girls with Rett normally have one healthy copy of the MeCP2 gene on one X chromosome that compensates for a mutated copy on the other X chromosome. Boys have one X chromosome. When a boy has a mutated copy of the MECP2 gene, he does not have the additional compensatory MeCP2 gene.
In the reported cases of males with MeCP2 mutations, patients develop signs of the disease at or shortly after birth.
Genetic analysis in the case of the boy in China revealed that he had a new mutation in MeCP2, known as p.Lys254. The MECP2 protein was truncated, or shortened, at amino acid 250. Amino acids are the building blocks of proteins.
Neither of the boy’s parents had this mutation. In male cases of Rett syndrome, most MeCP2 mutations are spontaneous, and occur in the division and formation of sperm.
The boy was small at birth given the duration of his mother’s pregnancy, and had a weak cry. His reaction was poor, and he had abnormal, shallow breathing and minimal movement. He required breathing support from a non-invasive ventilator.
Electroencephalograms (EEGs) found mild to moderate alterations in abnormal brain-wave patterns. No considerable improvements were observed in the span of three weeks. Immature sleep patterns were also noted on a brain-function assessment.
The boy showed alterations in both lungs, including a mild collection of fluid, and defects in valves separating heart chambers, causing blood to leak backwards. He also had too much carbon dioxide in his blood, as may happen when body cannot get rid of the carbon dioxide it creates.
The scientists compared blood proteins from the boy with those of three children his age. Results showed that 38 proteins were decreased and 69 proteins were increased in the boy with Rett. Seventy of these proteins were related to cellular processes, and 50 were related to metabolic processes.
In their analysis of protein interactions, the researchers found particular alterations in four proteins involved in the synthesis, or production, of arginine. Arginine is an amino acid that plays an important role in processes like cardiovascular and immune system functioning.
“Our results indicate that the arginine biosynthesis signal pathway may be the therapeutic target of MeCP2 syndrome,” the researchers wrote.
Several proteins related to heart muscle disease were also altered, they noted.
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