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Genes

Has anyone else been told this - You have Myotonia Congenita. However you have only one defective gene and the form you have has two defectives genes. There is something causing you to have MC, but we don't know what it is at this time.
I am going to a well recognized physician at a top facility, so I know what I am told is true.
Who else has been told this?
Thank you!
And Jan, what do you think of this?

Country: United States

Re: Genes

There are two main forms of chloride channel myotonia congenita is caused by mutations on the CLCN1 gene. This gene makes human skeletal muscle chloride channels. The little "doors" in the muscle cell wall, that let chloride into the cell to stop the muscle contraction. You inherit one CLCN1 gene from your mother, and another one from your father.

Thomsen Myotonia Congenita, which is dominant, meaning it only requires a mutation on one of your CLCN1 genes to manifest symptoms and so multiple generations of a family are usually affected, and Becker Myotonia Congenita, which is recessive and so requires a mutation on each of your CLCN1 genes.

But things aren't always so simple. With myotonia congenita, sometimes people have dominant mutations, but little or no symptoms. When this happens, the mutated gene is said to have incomplete penetrance. Likewise, sometimes people have only one recessive mutation, but still have symptomes.
There are a few reasons this might be.

1. Copy number variation. Where a segment of a gene gets copied and pasted back into the gene. One way you can think of this is imagine a normal gene to have this (imaginary) sequence
ABCDEFGHIJK.
Imagine the mutated gene to look like this.
ABCDJFGHIJK. The E has been replaced by a J.
Now imagine a mutated gene with a copy number variation to look like this. ABCDJFDJFGHIJK
The segment with the mutation, DJF, got copied, and pasted back into the gene. For some reason, this might effectively make the gene mutation express in a dominant form.

2. Modifier genes.
Genes are like machines in factors that print things out, and like all machines, they need instructions on when and how to operate. The things they print out also have to be processed, and transported. And there must also be instructions on how to do these things. These instructions are controlled by other genes, called modifier genes. Here is an analogy. Imagine you are a publisher and your printers always print out the same book. But as the publisher, you control when to print, what font to use, to print in black and white, or color, the size of the paper, and thus the size of the boxes, how to distribute them, and so on. You would be a modifier. There might be genes that can affect how often the mutated gene is used over the good gene, or other variables that make the mutated gene far more likely to be able to express.

3. Lab error or hidden mutations.
Our technology is not perfect. It's not impossible for labs to make mistakes, or for certain mutations and other gene anomalies to be missed.

4. Other factors.
Myotonia congenita has "high phenotype variability". This means there is a lot of variation on type and severity of symptoms. Some of this variation is caused by external and internal environmental factors. A person who's symptoms only manifest when they are cold, who lives in a warm climate all of their life, might never have symptoms. Some MC causing mutations have only been documented to cause symptoms during pregnancy, likely due to hormone levels. A man with these mutations might never have symptoms because he can't become pregnant, and thus the correct hormone levels to precipitate symptoms might never exist in his body.

It might be that it would be more appropriate from a technical and scientific standpoint, to call these recessive mutations, which are sometimes found to express in a dominant fashion, dominant genes with very low penetrance. But for practical reasons, it would be more appropriate to call them recessive.




Type of Myotonia: Becker

Country: USA

Re: Genes

Suzanne,

Jenna gave you a good explanation about dominant vs recessive and how it seems rules are made to be broken :-)

If you want to email me a copy of your DNA report I can check a database and see if your particular mutation has been associated with clinical symptoms. I can also ask a professional geneticist.

If you had your testing done at Athena, they have made mistakes in the past regarding the association of a mutation (dominant or recessive). Your doctor would know any differently...he's just going by the report.

Jan

Type of Myotonia: Thomsen's

Country: USA