What’s in Your LDS Family Tree? Genetics, Variability, Outcomes (September 1, 2020)
52:30-55:52
Can the mutation happen anytime in life or is it from birth only? I have a son with LDS2 and a healthy older daughter. My son is de novo so they had parental testing, I guess
MacCarrick:
遺伝子変異が起こるのは出生時のみでしょうか？それとも常に起こる可能性があるのでしょうか？LDS2型の息子と遺伝子変異のない娘がおります。息子さんはデノボ変異ということなので、ご両親も遺伝子検査を受けたということだと思いますね。
Year, so, mutations can be passed from parent to child by virtue of that change being in the cells that are making the egg cell or the sperm cell that are giving rise to that child that's what we call an inherited mutation. Mutation can occur during the formation of the egg cell or the sperm cell that go into the conception of a child so the parent doesn't have the change in any cell of their body but it was that one egg cell or one's one sperm cell that developed the change and then gave rise to a child with new Loeys-Dietz syndrome for that family.
Dietz:
卵子や精子を作る細胞内に遺伝子変異が存在することで、その変異が親から子へと受け継がれます。これが変異が遺伝する場合のしくみですが、卵子や精子が作られる途中で変異が生じ、その後受精することで、遺伝子変異をもった子どもが生まれることがあります。この場合、親の体内の細胞に全く変異がない場合でも、卵子や精子に偶然変異が生じたことで、家系内にLDSの子どもが誕生することになります。
Very, very, very, very rarely someone with a genetic condition has a change that occurred later in development typically not after they were born but when they were still forming in their mother's uterus but you know somewhere later on in the developmental process so they may only have the mutation in their blood and their skin where they may only have the mutation in their cardiovascular system but not in their skeleton that's something that's called a somatic mutation. It's exceedingly rare and unlikely to explain the situation that you're describing in your family. It's, if I understand your family correctly your affected child likely has a new change that was caused by a mutation or a DNA change in the egg cell or sperm cell that went into their conception and your other child, you know, did not develop that same change.
Dietz:
ほぼゼロに近い確率ではありますが、発育中に生じた変異により遺伝性疾患となる方もいます。とはいえ、この変異は、生まれた後ではなく、母親の子宮内で成長している最中に生じたものです。この場合、血液や皮膚、心血管系のみに異常がみられ、骨格系に影響はありません。こうした変異を体細胞変異と呼んでいます。極めて稀なケースですので、質問者さんの状況には当てはまらないと思われます。お話を聞いた限りでは、LDSの息子さんの場合、卵子や精子に生じた変異によって新規発症したものと思われます。娘さんでは同じ変異はみられないということでしたね。
You know, a good question, a good follow-on question is if I have a child with a new mutation that's causing a new case of Loeys-Dietz syndrome in my family is there any risk that I'm going to have another child affected with Loeys-Dietz syndrome with the same mutation?
Dietz:
こうした質問の後によくある質問として、LDSを新規発症した子どもが家系にいる場合、同じ変異の子どもが生まれる可能性があるか？というものがあります。
The answer is yes because occasionally a woman has the mutation in a population of cells just in their ovary or a man has the mutation just in a small population of cells in his testes so they don't have Loeys-Dietz syndrome themselves but there is a higher than zero risk that they will have another child with that same mutation because another egg cell or another sperm cell would be made that has that change that's something that's called germline mosaicism. It has been described for Loeys-Dietz syndrome but also rather uncommon.
Dietz:
回答はイエスです。母親の卵巣内の細胞の一部に変異がある、もしくは父親の精巣内の細胞の一部に変異があるといった場合、両親がLDSでなくとも、それらの細胞に生じたのと同じ遺伝子変異をもつ子どもが生まれる可能性があります。理由は、変異のある残りの細胞から卵子や精子が作られる可能性があるからです。こうした現象を生殖細胞系列モザイク現象と呼び、LDSでも可能性はあるとされていますが、やはり稀な事象です。
The Marfan Foundation did not participate in the translation of these materials and does not in any way endorse them. If you are interested in this topic, please refer to our website, Marfan.org, for materials approved by our Professional Advisory Board.
The Marfan Foundation は、当翻訳には関与しておらず、翻訳内容に関してはいかなる承認も行っておりません。このトピックに興味をお持ちの方は、Marfan.org にアクセスし、当協会の専門家から成る諮問委員会が承認した内容をご参照ください。
