目前已知有超過30個基因參與體重調控赋铝，這些基因一旦發(fā)生損傷性變化會導致極端肥胖情況的出現插勤。類似的，一些基因一旦出現變異可能導致人們患2型糖尿病革骨。目前科學界還不清楚因為遺傳而導致的極端肥胖和2型糖尿病到底占多大比例农尖，但是可以確定的是這些情況與囊胞性纖維癥和亨廷頓氏舞蹈癥一樣能夠遺傳。
倫敦大學皇家理工學院的研究人員近日發(fā)現了肥胖和2型糖尿病的一種新遺傳形式良哲。研究人員通過對一位極端肥胖的年輕女性及其家人的DNA進行排序盛卡，發(fā)現了這種新的缺陷基因。
這位女性從童年開始筑凫，因為食欲格外旺盛導致極度肥胖滑沧，患有2型糖尿病、學習困難癥并且面臨生育方面的問題巍实。工作人員發(fā)現一種突變的基因導致她不能合成一種名為羧基肽酶-E（CPE）的蛋白質滓技。CPE是一種酶，對許多激素以及大腦信號傳導的正常運行發(fā)揮重要作用蔫浆。而這些激素和大腦信號則控制著食欲殖属、胰島素以及其他在生殖系統(tǒng)中發(fā)揮重要作用的激素。
盡管已有證據證實CPE缺陷會導致小鼠肥胖瓦盛、糖尿病和記憶障礙洗显，但之前并沒有在人類中發(fā)現這種情況。因為CPE是一種隱性性狀玄组，一個人必須從他的父母親中都遺傳到一個變異的該基因才會受到影響滔驾。內分泌咨詢專家Tony Goldstone醫(yī)生哆致，曾為這名女性患者進行遺傳咨詢，得知患者的父母是表親胞此，這使她從雙親中遺傳到相同變異基因的可能性更高，另外她有一個患有相同病癥的哥哥在21歲時去世酣胀。
譯者解釋：
關于隱性性狀，科學的解釋大家可以去看書儒溉。通俗的來說就是下圖表現的。
B和b是控制相同性狀的基因涛碑，如B代表有酒窩，b代表沒酒窩揉阎，當B和b碰到一起時，B占上風烙如，性狀顯示仍然是有酒窩，這個時候b雖然存在但是其代表的沒有酒窩的性狀卻沒有表現出來刀闷。從圖中可以看出這對父母的子代有酒窩的可能性是75%顽分，沒有酒窩的可能性是25%雌隅。
bb碰到一起的概率在這種情況下本來就小，文中提到的女性患者，導致其肥胖的基因還是因為基因突變導致的吨枉，基因突變的隨機性很大认臊，所以碰到相同突變的2個隱性基因正好相遇其實并不是那么簡單。然而……近親后代遇到這種情況的可能性就大很多恕酸。這也是為什么我們不允許近親結婚的原因了。
負責此項基因測試同時也是該研究的第一作者Sanne Alsters博士稱凉翻，“為患者的病情找到一個遺傳原因可以幫助她和她的家庭更好的了解和處理她的病情。在她的親屬中制轰，有些人僅有一個該缺陷基因前计，我們可以對他們進行觀察男杈。僅有一個缺陷基因可能使他們獲得的肥胖風險沒有那么明顯伶棒⊥鸾ィ”
皇家理工學院醫(yī)學院教授鳍烁，也是這項研究的負責人Alex Blakemore表示：“目前被發(fā)現的可以導致的肥胖和糖尿病的單一基因越來越多幔荒。我們也不知道未來還會發(fā)現多少，也不知道極端肥胖人群中有多少比例的人們是患有這種疾病——因為我們僅通過肉眼觀察是無法分辨的梳玫∫”
“基因缺陷導致的肥胖是非常嚴重的失調情況，身體調節(jié)饑餓和飽腹信號的能力被影響盼忌。這種情況和其他遺傳疾病的遺傳機制是一樣的积糯〉嗄梗患者不應因此受到歧視，我們應該為他們提供遺傳咨詢和終身特別支持看成，使他們能夠盡可能的過上健康的生活君编。”Blakemore教授稱基因測序應該在極端肥胖的父母中被廣泛使用川慌。她說：“如果有人攜帶了某種可以導致肥胖的突變基因吃嘿，我們尋找攜帶可以導致其他病癥的突變基因的人，如果他們需要的話可以為他們和他們的家人提供遺傳咨詢梦重。對于患者來說這種診斷是非常有價值的兑燥。這將有助于設定符合現實情況的預期，也能幫助他們得到盡可能好的治療忍饰√吧”
該研究發(fā)表在公共科學圖書館期刊上，這個雜志是由英國國家健康研究所皇家生物醫(yī)學研究中心和英國糖尿病協會支持的艾蓝。
翻譯：朱曉倩 為了方便閱讀調整了一些段落順序
來源：Imperial College London. (2015, June 30). New genetic form of obesity, diabetes discovered. ScienceDaily. Retrieved July 1, 2015 from www.sciencedaily.com/releases/2015/06/150630080159.htm
Scientists have discovered a new inherited form of obesity and type 2 diabetes in humans.
A large number of genes are involved in regulating body weight, and there are now over 30 genes known in which people with harmful changes in DNA sequence become extremely overweight. Similarly, there are a number of genes that can, when altered, cause type 2 diabetes. These conditions are inherited through families in exactly the same way as disorders such as cystic fibrosis or Huntington's disease.
It is unclear what proportion of severe obesity and type 2 diabetes is caused by genetic disease.
Researchers at Imperial College London discovered the new defect by sequencing the DNA of an extremely obese young woman and members of her family. In addition to an increased appetite leading to severe weight problems from childhood, she had type 2 diabetes, learning difficulties, and reproductive problems.
They found that she had inherited two copies of a harmful genetic change that meant she could not make a protein called carboxypeptidase-E (CPE). This is an enzyme that is important in the proper processing of a number of hormones and brain transmitters controlling appetite, insulin and other hormones important in the reproductive system.
Studies have previously shown that CPE deficiency causes obesity, diabetes, and impaired memory in mice, but no humans with the condition have been found before. CPE deficiency is a recessive condition, so a person would need to inherit the altered genetic sequence from both parents to be affected.
The study, published in the journalPLOS ONE, was funded by the NIHR Imperial Biomedical Research Centre and Diabetes UK.
Professor Alex Blakemore from the Department of Medicine at Imperial College London, who led the study, said: "There are now an increasing number of single-gene causes of obesity and diabetes known. We don't know how many more have yet to be discovered, or what proportion of the severely obese people in our population have these diseases -- it is not possible to tell just by looking.
"These are serious disorders that affect the body's ability to regulate hunger and fullness signals. They are inherited in the just same way as other genetic diseases and the sufferers should not be stigmatised for their condition. They should be offered genetic counselling and specialised lifelong support to allow them as healthy a life as possible."
The patient was clinically evaluated by consultant endocrinologist Dr Tony Goldstone, who runs a specialist genetics obesity clinic at Hammersmith Hospital. The patient's parents are cousins, giving her a relatively high likelihood of inheriting the same genetic change from both parents. She had an older brother with similar symptoms who died aged 21.
The first author Dr Sanne Alsters, also in the Department of Medicine, who carried out the genetic tests, said: "Finding a genetic cause for the patient's problems has helped her and her family to understand and manage her condition better. We can also look at members of her family with one abnormal copy of the gene, to see they are affected in more subtle ways that could increase their risk of obesity."
Professor Blakemore said genetic tests should be widely available for patients with severe obesity. "If people are diagnosed with a genetic condition like this one, we can look for other possible symptoms, and offer genetic advice to other family members if they want this. Diagnosis is very valuable to the patient. It helps to set realistic expectations, and can help them get the best possible treatment," she said.
