EMMA'S MUTATION EXPLORED

During the genetic examination, the following mutation was found in Emma.

What does it all mean? And, more importantly, what can we do about it?

"De novo" means newly occurring, not inherited from parents.

Mutation: c.1642C>T

• This notation describes a specific change in the nucleotide sequence of a gene.
"c" indicates that it's a mutation at the nucleotide (DNA) level.
• "1642" represents the position in the nucleotide sequence where the change occurred.
• "C" represents the original nucleotide at this position.
• "T" represents the new nucleotide that appeared due to the mutation.

Protein change: p.(Arg548Cys)

• This part of the description tells us what change occurred at the amino acid level in the protein encoded by the CHAMP1 gene.
• "p." stands for protein change.
• "Arg548" denotes the original amino acid at position 548 in the protein, which was arginine (Arg).
• "Cys" denotes the new amino acid that replaced the original one, which is cysteine (Cys).

WHAT CAN BE DONE?

Although there are only about 150 children in the world with a similar mutation, genetic research is underway in the USA, Europe, and Japan with the aim of either turning off the gene using CRISPR or disrupting the production of the protein (using ASO). It is becoming evident that people without this gene are significantly better off than those with the mutation.

GENE THERAPY

The most promising possibility is the gene therapy approach, which involves introducing functional copies of the CHAMP1 gene into a patient's cells to replace the mutated or non-functional gene. This method should correct the damage caused by the mutated CHAMP1 gene. To facilitate this process, a gene therapy vector is employed as a delivery system, ensuring that the healthy CHAMP1 gene is effectively transported to target tissues, such as the brain and spinal cord.

ASO (Antisense Oligonucleotides)

ASOs are molecules of DNA or RNA designed to bind to specific genetic sequences. Their primary purpose is to influence gene expression by interfering with the process of protein production encoded by that gene. In the context of the research mentioned, ASOs are used to disrupt the production of the protein associated with gene mutations that cause diseases. This aims to reduce or completely halt the production of harmful proteins and improve patients' health.

CRISPR:

CRISPR is a groundbreaking technology that allows precise modification of genetic material in cells. It relies on molecular tools that enable the targeting and precise editing of specific genes in the genome. This is done using RNA molecules that guide enzymes to specific locations in DNA, allowing cells to repair or modify genetic material. In the mentioned research, CRISPR is used for targeted gene silencing or editing of specific genes associated with disease-causing mutations. This can potentially eliminate or correct genetic variants that lead to pathological conditions.

Go,

EMMA!