Machens Andreas, Dralle Henning
Department of General, Visceral and Vascular Surgery, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
Clin Endocrinol (Oxf). 2008 Jul;69(1):81-7. doi: 10.1111/j.1365-2265.2007.03153.x. Epub 2008 Jul 1.
No comprehensive information exists nationwide about the familial prevalence and age of rearranged during transfection (RET) germline mutations. The current investigation was undertaken to provide such natural history data which are urgently needed to enable factual decision-making about DNA-based screening programmes for RET germline mutations.
Descriptive study drawn on countrywide referrals to a specialist surgical centre.
Included were 452 patients from 141 German RET families: 277 carriers referred for pre-emptive or therapeutic surgery, and 175 additional carriers or relatives with endocrine tumours associated with multiple endocrine neoplasia type 2 (MEN2).
Key variables included familial prevalence, phenotype and latest year of birth of RET germline mutations. RESULTS A total of 26 different RET germline mutations were identified among the 141 RET families: C634R (21%); M918T (15%); C634Y (9%); L790F/TTG-->TTT (8%), Y791F (7%), V804M (6%); C620R and C634F (5% each); L790F/TTG-->TTC and C634S/TGC-->TCC (4% each); C618S/TGC-->AGC, C634G and S891A (2% each); C618F and E768D (1% each); and in < 1% each: C609G, C611F, C611Y, C618G, C618Y, C620S/TGC-->AGC, C620S/TGC-->TCC, C620Y, C630R, D631Y and V804L. Most of these differences in prevalence rates, seemingly, were caused by recent spontaneous mutations in the germline. With rare exceptions, longstanding transmission was noted in at least one RET family per affected codon. Many germline mutations were traceable back to the early 20th, and a few even to the 19th century.
These data reveal the potential of DNA-based screening of all relevant RET exons, especially for index patients with solitary, seemingly sporadic disease.
全国范围内尚无关于转染期间重排（RET）种系突变的家族患病率和年龄的全面信息。目前的调查旨在提供此类自然史数据，这些数据对于就基于DNA的RET种系突变筛查计划做出实际决策至关重要。
基于全国范围内转诊至一家专业外科中心的描述性研究。
纳入了来自141个德国RET家族的452名患者：277名携带者因预防性或治疗性手术前来就诊，另有175名携带者或亲属患有与2型多发性内分泌肿瘤（MEN2）相关的内分泌肿瘤。
关键变量包括RET种系突变的家族患病率、表型和最晚出生年份。结果在141个RET家族中总共鉴定出26种不同的RET种系突变：C634R（21%）；M918T（15%）；C634Y（9%）；L790F/TTG→TTT（8%），Y791F（7%），V804M（6%）；C620R和C634F（各5%）；L790F/TTG→TTC和C634S/TGC→TCC（各4%）；C618S/TGC→AGC、C634G和S891A（各2%）；C618F和E768D（各1%）；以及各<1%：C609G、C611F、C611Y、C618G、C618Y、C620S/TGC→AGC、C620S/TGC→TCC、C620Y、C630R、D631Y和V804L。这些患病率的差异似乎大多是由种系中近期的自发突变引起的。除极少数例外，每个受影响密码子至少在一个RET家族中观察到长期传递。许多种系突变可追溯到20世纪初，少数甚至可追溯到19世纪。
这些数据揭示了对所有相关RET外显子进行基于DNA筛查的潜力，特别是对于患有孤立性、看似散发疾病的索引患者。
