Toogood A A, Eng C, Smith D P, Ponder B A, Shalet S M
Department of Endocrinology, Christie Hospital NHS Trust, Manchester, UK.
Clin Endocrinol (Oxf). 1995 Dec;43(6):759-62. doi: 10.1111/j.1365-2265.1995.tb00547.x.
Multiple endocrine neoplasia type 2B (MEN 2B) is a rare cancer syndrome which is inherited in an autosomal dominant manner. The molecular basis of this condition has recently been defined as a mutation of codon 918 of exon 16 of the RET proto-oncogene. The mutation in codon 918 has been described in 69 out of 72 families with MEN 2B. We have studied a brother and sister who undoubtedly have the features of MEN 2B as evidenced by medullary thyroid carcinoma, phaeochromocytoma, mucosal neuromas and skeletal abnormalities. Neither of these patients has the classic gene mutation at codon 918 of exon 16 of the RET proto-oncogene, and although exons 2-20 have also been sequenced, no abnormality has been found. DNA analysis is a sensitive method of screening families for the MEN 2 syndromes. The absence of the mutation at codon 918 in a phenotypically normal individual would refute the diagnosis of MEN 2B, but in an individual with some of the features of MEN 2B would make the clinician reconsider the diagnosis. This family demonstrates that, although it is rare, the absence of the mutation in codon 918 of exon 16 of the RET proto-oncogene does not always exclude the diagnosis of MEN 2B. In such families routine biochemical screening for medullary thyroid carcinoma and phaeochromocytoma must be maintained for all individuals at genetic risk.
2B型多发性内分泌腺瘤病（MEN 2B）是一种罕见的癌症综合征，以常染色体显性方式遗传。这种疾病的分子基础最近被确定为RET原癌基因第16外显子密码子918的突变。在72个患有MEN 2B的家族中，有69个家族描述了密码子918的突变。我们研究了一对兄妹，他们无疑具有MEN 2B的特征，如甲状腺髓样癌、嗜铬细胞瘤、黏膜神经瘤和骨骼异常。这两名患者均未在RET原癌基因第16外显子密码子918处出现经典基因突变，并且尽管对第2至20外显子也进行了测序，但未发现异常。DNA分析是筛查家族中MEN 2综合征的一种敏感方法。在表型正常的个体中，密码子918处无突变将排除MEN 2B的诊断，但在具有某些MEN 2B特征的个体中，这将使临床医生重新考虑诊断。这个家族表明，尽管罕见，但RET原癌基因第16外显子密码子918无突变并不总是排除MEN 2B的诊断。在这类家族中，必须对所有有遗传风险的个体进行甲状腺髓样癌和嗜铬细胞瘤的常规生化筛查。
