MECP2 Duplication Carrier Status: Part 1

XxThis is a topic that I have been somewhat reluctant to write about for couple of reasons. First, since this is something that directly affects women, perhaps a woman’s perspective would be more appropriate. Second, while there is some interesting information that has emerged on this topic, most of it is fairly tentative at this point, and there are few well-established facts. Nevertheless, there have been a couple of recent developments that make me feel that this might be a good time to summarize some of the information that is available. First, because some women in affected families have been requesting this information. Second, because a recent research article has helped shed a little more light on the topic. So, I will try to summarize some of the available information here.

Who are carriers?

In most cases, the mothers of BOYS with MECP2 Duplication Syndrome also share exactly the same duplication on one of their two X chromosomes. This is not usually the case for most girls with MECP2 Duplication Syndrome. Since the mothers who carry this duplication do not have the major symptoms, we do not say that have the syndrome, but because they can pass the duplication on to their offspring, we refer to them as carriers.

Of course, some women who are carriers do not have sons with the syndrome. If a carrier has a son, there is only about a 50% chance that he will have this syndrome. Some would argue that the chances are even a bit less than 50% for reasons explained later. In the vast majority of cases, daughters of carriers will not have the syndrome, although there can be rare exceptions, however, there is 50% chance that daughters will also get the duplication and be carriers.

Why don’t carriers have major symptoms of the syndrome?

Because females have two X chromosomes and always inactivate one in each cell, they can protect themselves by selectively inactivating the X with an extra copy of MECP2. In most cases, some process allows the body to detect the X chromosomes with the extra MECP2 and selectively inactivate it. This is sometimes referred to skewing, and in most cases females carriers are able to selectively inactivate nearly 100% of the Xs with the duplication.

Can men be carriers?

Men cannot be carriers in this sense. Since men only have one X chromosome, they can not inactivate it. If they have the duplication, they will have the syndrome. To the bast of my knowledge, no male with the syndrome has fathered children, so they do not pass it on. If a man who had the syndrome fathered children, boys would presumably be unaffected, because men do not pass an X chromosme to their sons (the exception might be if the duplication was translocated to another chromosome. If they fathered a girl, she presumably would be a carrier, since she would get the affected X from her father.

This is Part 1 of a series.  . Part 2: “Do Carriers have symptoms” will follow



6 responses to “MECP2 Duplication Carrier Status: Part 1

  1. Hello, have you posted part 2 yet? This is wel done. Very interesting!

    • I haven’t posted part 2 yet. Got distracted by some otehr topics, but thanks for prompting me, I’ll try to get it out in the next week or so,

      • Sure! You sound very knowledgeable. I have recently been found to be a mecp2 carrier and my son has a missense mecp2 alteration along with a syngap1 mutation. So this topic speaks to me. I wondered if there are things in my health I should be looking out for… just browsing around online. 🙂 thank you!

  2. Hi Lauren, I wish I could provide a clear answer to your question, but I really can’t for three reasons. 1. most of what I might say about carriers of MECP2 duplications remains largely untested, there have been only very preliminary studies on carriers and the results are quite tentative. 2. a missense mutation of MECP2 is quite different from a duplication, and may or may not have similar effects in carriers. So I think you would need to be extra careful in applying this to yourself. 3. Because there are two “suspect” genes, it is hard to sort out whether any symptoms result from one, the other, or a combination. If he fits the clinical picture of boys with Rett or if not, that might help sort it out.

    • Thank you for mentioning that there is a difference between missense and duplication. l didn’t even consider that. I had to look up missense. The genetic counselor didn’t really touch on mecp2 at all, other than to say that it was of unknown significance. My son does definitely identify strongly with the syngap1 mutation features. Thank you for this information and responding to me!

  3. Some MECP2 mutations have little effect on the function of the gene and others in rare in boys. If the symptoms don’t look much like Rett syndrome, it is likely that the MECP2 mutation is not responsible or only contributes a little to his condition. If that is the case, it is unlikely that this mutation would affect you as a carrier, because females have two copies of the X, so any small effect in a male is likely to be much smaller in a female with one mutated and one normal gene. But I am sure that a genetic counselor could provide much better advice, so if this is a concern for you, you should discuss it with your doctor.

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