When your child is diagnosed with NKH, a genetic test will be sent off the confirm the diagnosis. It takes 2-3 months to come back, and when you get the letter it can be very confusing.
There are several different kinds of mutations:
This is a single point mutation where a single nucleotide (one rung on the dna ladder) has mutated. This causes a codon which creates a different amino acid than was intended.
This is also a single point mutation, but with the single nucleotide mutation, it creates a premature stop codon, or a premature stop codon in the transcribed mRNA. This causes a truncated/incomplete protein which can’t be used.
This is where a part of a chromosome or a sequence of DNA is lost during DNA replication.
This is where the mutation inserts, deletes or changes a number of nucleotides in the spot where a splicing takes place (while processing of precursor messenger RNA).
It’s helpful to know that each rung on the DNA ladder (called nucleotides) contributes to a set of three – called a codon. All the amino acids are made up a codon.
- GCA is the codon for alanine
- AGA is the codon for arginine
- TCA the codon for serine
There are 64 possible codons, but only 20 amino acids, so more than one codon may code for a single amino acid. For example, GCA, GCC, and GCG all mean alanine. You can view the codon table here.
If your genetic code switches one of those nucleotides because of a mutation in the gene, the codon will make a different amino acid.
- TCA the codon for serine
- The mutation switches the second C for a T
- TTA the codon for Leucine
- Where the glycine cleavage system is expecting serine, it’s now getting Leucine, and the protein is now nonfunctional.
That is the essence of a missense mutation.
When you’re given a genetics laboratory report, it can be confusing to understand. But there will be a panel result. It may look like this:
GLDC: c.395C>T; p.(Ser132Leu)
To break down into easier to understand parts:
- GLDC – This is gene the mutation was found it. Typically NKH mutations are found in the GLDC gene or the AMT gene
- c.1108 – This is the codon location within the gene of where the mutation can be found
- C>T – This is the mutation. Where the nucleotide should use C (Cystosine), T (Thymine) is being used instead.
- p.(Ser132Leu) – This is the protein created as a result of the mutation. Where Seriene (Ser) was expected, Leucine (Leu) is now being created instead. 132 is the location where this is happening. Side note: this reflects the codon of the mutation. If you divide 395/3 (for the three nucelotides in the codon) you’ll get the location of the protein. Example 395/3 = 132. They point to the same place in the gene.