應用胚胎著床前基因診斷克服遺傳性腓骨肌萎縮症第IIE型：世界第一例 Preimplantation genetic diagnosis of Charcot-Marie-Tooth disease Type IIE: Report of the first successful case in the literature 蔡鋒博*1, 陳昭雯1, 林招彰1,張舜評2,3, 馬國欽2, 陳明2,3,4,5 1博元婦產科診所 試管嬰兒中心 2 彰化基督教醫院 基因醫學部 3中興大學 生命科學系 4台灣大學 醫學院婦產部 5東海大學 生命科學系 <2012 annual meeting agenda-.doc> http://www.tsrm.org.tw/word/2012/0807/all_abstracts%20_O01_29.P01_31.pdf http://www.tsrm.org.tw/word/2012/0807/%E5%85%A8%E9%83%A8abstract%E6%96%87%E7%AB%A0.pdf P02 應用胚胎著床前基因診斷克服遺傳性腓骨肌萎縮症第 IIE 型：世界第一例 Preimplantation genetic diagnosis of Charcot-Marie-Tooth disease Type IIE: Report of the first successful case in the literature 蔡鋒博*1, 陳昭雯 1, 林招彰 1, 張舜評 2,3, 馬國欽 2, 陳明 2,3,4,5 1 博元婦產科診所 試管嬰兒中心 2 彰化基督教醫院 基因醫學部 3 中興大學 生命科學系 4 台灣大學 醫學院婦產部 5 東海大學 生命科學系 Feng-Po Tsai1, Chao-Wen Chen1, Chao-Chang Lin1, Shun-Ping Chang2,3, Gwo-Chin Ma2, Ming Chen2,3,4,5 1 Poyuan Women Clinic, IVF centre, Changhua, 2 Department of Genomic Medicine, Changhua Christian Hospital, Changhua, 3 Department of Life Sciences, National Chung-Hsing University, Taichung, 4 Department of Obstetrics and Gynecology, National Taiwan University, Taipei, 5 Department of Life Sciences, Tunghai University, Taichung, Introduction: Charcot–Marie–Tooth disease (CMT), also known as Charcot–Marie–Tooth neuropathy, hereditary motor and sensory neuropathy (HMSN) and peroneal muscular atrophy (PMA) — is a genetically and clinically heterogeneous group of inherited disorders of the peripheral nervous system characterised by progressive loss of muscle tissue and touch sensation across various parts of the body. It is one of the most common inherited neurological disorders worldwide, affecting approximately 1 in 2,500 people. CMT is caused by mutations that cause defects in neuronal proteins. Nerve signals are conducted by an axon with a myelin sheath wrapped around it. Most mutations in CMT affect the myelin sheath, but some affect the axon.CMT is divided into the primary demyelinating neuropathies (CMT1, CMT3, and CMT4) and the primary axonal neuropathies (CMT2), with frequent overlap. Symptoms of CMT usually begin in late childhood or early adulthood. Some people do not experience symptoms until their early thirties or forties. Usually, the initial symptom is foot drop onset early in the course of the disease. This can also cause claw toe, where the toes are always curled. Wasting of muscle tissue of the lower parts of the legs may give rise to a "stork leg" or "inverted bottle" appearance. Weakness in the hands and forearms occurs in many people later in life as the disease progresses. Loss of touch sensation in the feet, ankles and legs, as well as in the hands, wrists and arms is characteristic in various types of the disease. Early and late onset forms occur with 'on and off' painful spasmodic muscular contractions that can be disabling when the disease activates. High arched feet (pes cavus) are classically associated with the disorder. Sensory and proprioceptive nerves in the hands and feet are often damaged, while pain nerves are left intact. Overuse of an affected hand or limb can activate symptoms including numbness, spasm, and painful cramping. CMT2E is transmitted in an autosomal dominant manner and maps to chromosome 8p21. We presented a couple with CMT2E seeking for preimplantation genetic diagnosis. Material & methods: Parental genetic analysis showed the paternal heterozygous mutation was c.23C>G (p.P8R) in the exon 1 of NEFL gene. We developed and evaluated an in-house duplex-nested ARMS-qPCR, and to compare it to the direct sequencing, considered to be the gold standard. The optimized protocol was then applied clinically to detect the disease-causing mutations in embryos acquired after ovarian stimulation. 7 fertilized oocytes were developed into embryos useful for biopsy. 4 unaffected embryos were transferred, resulting in a triplet pregnancy. Discussion: This is the first successful case of CMT 2E-affected family usingPGD to prevent the transmission of the disease-carrying gene. We wish this experience will be helpful for other families who also suffered from other hereditary diseases with known gene loci. 世界首例！基因晶片篩檢　終結百年遺傳病 http://www.appledaily.com.tw/realtimenews/article/life/20120825/139250/applesearch/%E4%B8%96%E7%95%8C%E9%A6%96%E4%BE%8B%EF%BC%81%E5%9F%BA%E5%9B%A0%E6%99%B6%E7%89%87%E7%AF%A9%E6%AA%A2%E3%80%80%E7%B5%82%E7%B5%90%E7%99%BE%E5%B9%B4%E9%81%BA%E5%82%B3%E7%97%85 腓骨肌萎縮症（CMT）。翻攝網路 字級： 最小字型預設最大字型 分享到 Facebook分享到 Plurk分享到 Twitter 2012年08月25日17:55 31歲白先生，家族自奶奶、爸爸共3代近百年，患有遺傳性腓骨肌萎縮症（CMT），12歲發病後走路跛腳、經常跌倒，今年2月夫妻決定人工受孕，彰基基因醫學部主任陳明，先抽血找出CMT2E型基因異常位點，經基因晶片過濾掉受精卵異常胚胎後（顯性遺傳疾病的胚胎異常機率約50％），再將正常胚胎植入母體，終結罕病遺傳宿命，目前已懷有一對健康雙胞胎23周。 陳明表示，基因晶片過濾基因異常胚胎，技術愈來愈成熟，也可運用在其他遺傳疾病胚胎篩檢。但克服遺傳性腓骨肌萎縮症是世界首例，〈應用胚胎著床前基因診斷克服遺傳性腓骨肌萎縮症：世界第一例〉論文，今在台灣生殖醫學會年會中發表。 世界第一例: 博元婦產科以晶片試管嬰兒克服CMT周邊漸凍人終結白家近百年遺傳病生下鍵康雙胞胎 http://youtu.be/-bysWdwGLFE 華視 報導博元婦產科試管嬰兒新技術：世界首例！ 胚胎基因診斷 擺脫遺傳肌萎症 【2012/8/25 20:15】用於篩檢遺傳性腓骨肌萎縮症，史無前例, 世界首例！PGD挽救週邊漸凍人「生」機,博元婦產科院長蔡鋒博醫師和彰基基因醫學部陳明醫師共同發表 博元婦產科以晶片試管嬰兒克服CMT周邊漸凍人終結白家近百年遺傳病生下鍵康雙胞胎 華視 報導博元婦產科試管嬰兒新技術：世界首例！ 胚胎基因診斷 擺脫遺傳肌萎症 【2012/8/25 20:15】用於篩檢遺傳性腓骨肌萎縮症，史無前例, 世界首例！PGD挽救週邊漸凍人「生」機,博元婦產科院長蔡鋒博醫師和彰基基因醫學部陳明醫師共同發表 博元婦產科以晶片試管嬰兒克服CMT周邊漸凍人終結白家近百年遺傳病生下鍵康雙胞胎 http://youtu.be/-bysWdwGLFE http://youtu.be/-bysWdwGLFE