Carlson K M, Bracamontes J, Jackson C E, Clark R, Lacroix A, Wells S A, Goodfellow P J
Division of Human Molecular Genetics, Washington University School of Medicine, St. Louis, MO 63110.
Am J Hum Genet. 1994 Dec;55(6):1076-82.
Multiple endocrine neoplasia type 2B (MEN 2B) is characterized by medullary thyroid carcinoma, pheochromocytomas, mucosal neuromas, ganglioneuromas, and skeletal and ophthalmic abnormalities. It is observed as both inherited and sporadic disease, with an estimated 50% of cases arising de novo. A single point mutation in the catalytic core region of the receptor tyrosine kinase, RET, has been observed in germ-line DNA of MEN 2B patients. We have analyzed 25 cases of de novo disease in order to determine the parental origin of the mutated RET allele. In all cases the new mutation was of paternal origin. We observe a distortion of the sex ratio in both de novo MEN 2B patients and the affected offspring of MEN 2B transmitting males. These results suggests a differential susceptibility of RET to mutation in paternally and maternally derived DNA and a possible role for imprinting of RET during development.
2B型多发性内分泌腺瘤病（MEN 2B）的特征包括甲状腺髓样癌、嗜铬细胞瘤、黏膜神经瘤、神经节瘤以及骨骼和眼部异常。它既可表现为遗传性疾病，也可表现为散发性疾病，估计有50%的病例为新发。在MEN 2B患者的生殖系DNA中观察到受体酪氨酸激酶RET的催化核心区域存在单点突变。我们分析了25例新发疾病病例，以确定突变的RET等位基因的亲本来源。在所有病例中，新突变均来自父系。我们观察到新发MEN 2B患者以及MEN 2B传递男性的受影响后代的性别比例存在偏差。这些结果表明RET在父系和母系来源的DNA中对突变的易感性不同，并且在发育过程中RET可能存在印记作用。
