Kabuki Syndrome Network in Japan Newsletter歌舞伎ジャーナル 第２４号
１１月７日に全米遺伝学会でDr. Milunsky が発表された内容の要約(一般向け・英文)
〜要約文作成は,北米ネットワークの事務局マーゴット(トップページの女の子のお母さん)さんです。とりあえず原文を掲載します。後日翻訳をします。また,Dr. Milunskyの発表文章(英文)を入手したい方はメールをください。Word 書式でお送りします。〜
Dr. Milunsky and colleagues found a duplication on part of one of the 8th chromosomes of an initial sampling of individuals with Kabuki. The exact region of the chromosome is 8p22-23.1. It has also been discovered that two out of two mothers of these six initial cases have an inversion on their 8th chromosome in the region of 8p23.1. (See Note below) Further studies revealed that all six individuals with Kabuki have inherited their mother’s inversion at 8p23.1. The fathers’ chromosomes did not appear to have any abnormalities.
Humans have 46 chromosomes (23 pairs) in each cell. Of these, 23 came from our mother and 23 from our father. Scientists have numbered the chromosomes from the largest (chromosome 1) to the smallest (chromosome 22). These numbered pairs are also sometimes called autosomes. The last pair of chromosomes are called the sex chromosomes. (See figure 1) A chromosome is made up of a short arm (at top) called p arm and a long arm (at bottom) called q arm. The two arms are divided by a constricture called the centromere. (See figure 2)
Each chromosome is made up of long strings of DNA. Each of these strings is called a gene and they each have their own specific location on the chromosome. Since chromosomes come in pairs, so do our genes. It is estimated that each cell contains about 30,000 pairs of genes.
Each gene is a ‘package’ of information, a recipe for an essential component or function of our body. They cause the production of proteins or a chain of protein’s building blocks called amino acids. When a cell requires a particular protein, the message from the required gene is ‘read’ for that function. Once the message is interpreted and transcribed, it is now known as a protein. Some of the proteins, such as keratin from which hair is made, are the building blocks for particular structures, other are called enzymes which help carry out chemical reactions such as digesting food, and yet others form communication networks within and between cells. Since the body has many different types of cells such as those in the muscles, heart, and brain, not all cells require the same proteins to function correctly. That is why only the necessary genes are activated or ‘turned on’ for that particular cell. Some genes are only active at certain times of our development, such as during fetal development, and then are ‘switched off’ since their function is complete.
When the genetic code is changed due to a mutation, an alternate message is given to the cells. Some changes don’t make a difference to the way the message is read. Other changes cause a message not to be read correctly or not read at all. These faulty genes may cause problems with the function or development of various body systems and can result in a genetic disorder.
Back to Kabuki:
In the case of Dr. Milunsky’s findings, part of one of the 8th chromosomes has a very small area of duplicated material. When we read duplication at 8p22-23.1, this defines that the added chromosomal material takes place on one of the 8th chromosome pair, on the p arm of the chromosome (upper), and at the precise region of 22-23.1. Because there is a duplication, there are too many genes in this particular area of the chromosome, which means the messages transcribed to the cells particular for those genes are incorrect. Because Kabuki has such a varied range of characteristics, it is likely that not every child has duplication of the exact same genes in that area. With further studies we hope to discern which genes are involved, in the hopes that we can be more specific in predicting what kinds of characteristics are likely for each child.
An inversion occurs when a piece of a chromosome breaks off, gets twisted around (spins on its axis) and then reconnects in reverse order. (See figure 3) In most cases, as long as material was not lost or the split did not happen in a gene (interfering with the function of that gene), the individual with the inversion should have no problems since all the genetic material is still there. However, the offspring of that individual has an increased risk of abnormalities due to an imbalance of chromosomal material.
Back to Kabuki:
The article states that analysis was also performed on the chromosomes of two sets of available parents. Both mothers revealed an inversion of 8p23.1. This defines that the inversion took place on one of the 8th chromosome pair, on the p arm of the chromosome (upper), and in the precise region of 23.1. The father’s chromosomes did not show any abnormalities. Subsequent further analysis showed that all six of the children with Kabuki inherited the identical submicroscopic (very small) inversion at 8p23.1.
Since the submission of the article, the remaining four mothers of these initial six cases have all shown the same inversion at 8p23.1.
Figure 1Figure 2 Figure 3
Comments from Dr. Milunsky:
We are very excited about our initial findings and very grateful to the Kabuki Syndrome Network and all of our participating families. The next step in our research is to narrow the critical Kabuki syndrome region and identify the specific genes that are duplicated (or otherwise altered) that result in the diverse clinical findings of Kabuki syndrome. To accomplish this, we need more Kabuki syndrome families to be enrolled in our studies. These studies remain in the research laboratory and should not be offered on a clinical basis at this time until further validation and accurate interpretation are achieved. We look forward to continuing our work with Kabuki Syndrome Network families. Your help has been invaluable.