Inheritance
This condition is passed down through the X chromosome (X-linked). Since males have only one X chromosome, they are more likely to show symptoms if they inherit the faulty gene. Female carriers of a pathogenic variant don’t have symptoms, but have a 50% chance of passing the gene to their sons, who would then be affected.
Genetic testing
The genetic testing can be arranged by a clinical geneticist and involves the collection of a sample of blood or saliva from the affected individual (and eventually the parents). The tests can include:
• Single-gene testing – in case the individual’s characteristics raise the suspicion of the -linked condition
• Targeted gene panel testing - testing a group of genes linked to similar conditions.
• Exome sequencing – scanning all protein-coding genes in case the clinical picture is not specific
Suspected pathophysiologic mechanism
The gene makes a protein called the gamma (γ) subunit of a larger protein complex called eIF2. This complex is very important because it helps start the process of making new proteins in our cells. Regulation of eIF2 is used in cells to respond to stress. For example, when there are too many unfolded proteins, regulation of eIF2 slows down overall protein production to help the cell cope.
If the gamma subunit of eIF2 doesn’t work properly, the cell can start making proteins at the wrong places on the mRNA, leading to mistakes. Also, the cell cannot make enough proteins overall, which especially affects cells that need to produce a lot of proteins quickly. This can cause problems in organs and tissues that have high energy and protein demands.
EIF2S3