Sunday 7 May 2017

A quick genetics lesson

I am aware that the past few posts have been quite heavy, they have been hard to write and I know some of you have found them hard to read.  So now for a little light relief with some science (HA!)

I mentioned in a previous post that Alfie’s condition is genetic.  An initial diagnosis was given to us before we had any genetic testing done.  The initial diagnosis was a keratin 1 mutation because during the first week the skin on Alfie’s palms and soles had peeled.  During our first appointment at Birmingham Childrens Hospital when Alfie was about a month old, blood was taken and was sent off to Dundee for testing.  We were told that the results could take up to a year to come back.  The results actually came back a few months later but reported a mutation on the kertatin 10 gene and not 1 as first thought – meaning that his palms and soles were not affected.

Different type of ichthyosis are caused by errors on different genes.  Genes can either be inherited autosomal recessively,  autosomal dominantly or x-linked and to try to explain this I will use 3 examples: EI (Alfies type of ichthyosis), Lamellar Ichthyosis (LI) and x-linked ichthyosis (XLI). 

In LI, the genes that cause the condition are inherited recessively.  Both parents need to be a carrier of the gene (and will not necessarily have the condition themselves). Any child they have has a 25% chance of presenting with the condition, a 50% of their child carrying the gene and a 25% chance of them not passing the gene on at all.  Because the gene is recessive, in order to inherit the condition the child would need to have a copy of the gene from both parents. 

In XLI the mutation is present on the X chromosome only and is passed on from the mother.  The majority of people affected by this type of ichthyosis are male.  This is because females inherit 2 X chromosomes (one from mother and one from father)  and the unaffected chromosome compensates for the affected one.  Males carry an X and a Y chromosome so if the male inherits the affected X chromosome from their mother, they will present with the condition because they do not have an additional unaffected X chromosome to compensate for it.  When a mother is a carrier, any daughters they have will have a 50% chance of being a carrier and any sons have a 50% chance of being affected.  Fathers that are affected by XLI will not pass this on to their sons because they only pass the Y chromosome on but daughters will have a 50% chance of being a carrier.


In EI (Alfie’s type), the genes that are responsible for causing the condition are dominant which means that only one parent has to carry the gene for it to be passed on.  As the affected gene is dominant, the carrier is affected.  If someone with EI goes on to have children, their child will have a 50% chance of also having the condition. 

Just to confuse matters even more, those of you that know us will know that neither Lee or I have EI which means we don’t carry the mutated gene.  So how did Alfie end up with it if we haven’t passed it down to him?  After his diagnosis was confirmed, we were sent to see a geneticist.  He explained that in a small number of EI cases, the parents do not present with widespread ichthyosis but sometimes have a small patch on their skin.  On examination, neither of us had this...i was confused!!  He then went on to explain that in a lot of EI cases, the condition is caused by a random mutation on the keratin gene and no one knows how or why it happens.  You can think of it as a kind of typo on the gene when it is being copied.  So in our case, as neither parent has the condition or has a small patch that could have caused it, we assume that it is just a random thing that happened to Alfie before he was born.   We don’t know why the random mutations happen or what may have caused it.   Since Alfie does have EI, any children he goes on to have would have a 50% chance of inheriting it from him.  If he had children that were not affected then that is where the genetic inheritance would end (unless there was another random mutation).

Baffled? Me too although my A-level biology teachers would be so proud that I finally took an interest!


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