Marsh D J, Robinson B G, Andrew S, Richardson A L, Pojer R, Schnitzler M, Mulligan L M, Hyland V J
Molecular Genetics Unit, Kolling Institute of Medical Research, Royal North Shore Hospital, St. Leonards, New South Wales, Australia.
Genomics. 1994 Sep 15;23(2):477-9. doi: 10.1006/geno.1994.1526.
Multiple endocrine neoplasia type 2A (MEN2A) and familial medullary thyroid carcinoma (FMTC) are autosomal dominant inherited cancer syndromes with incomplete penetrance. Following the identification of mutations in the RET proto-oncogene that segregate with the disease phenotype in MEN2A, MEN2B, and FMTC, genetic screening of individuals with mutations in RET may be performed. We have employed restriction endonuclease digestion of polymerase chain reaction products as an alternative to sequence analysis for rapid identification of mutant gene carriers in families in which MEN2A and FMTC are segregating. Twenty-one Australasian MEN2A and FMTC families have been screened for mutations in a cysteine-rich region of the RET proto-oncogene. Seven independent mutations were identified in key individuals in 16 of these families. We have identified a mutation in codon 620, 2053 T-->C (Cys620Arg), and two mutations in codon 634 of exon 11 of RET, 2095 T-->C (Cys634Arg) and 2096 G-->A (Cys634Tyr), all three of which were present in both MEN2A and FMTC families.
2A型多发性内分泌腺瘤病（MEN2A）和家族性甲状腺髓样癌（FMTC）是常染色体显性遗传的癌症综合征，具有不完全外显率。在确定RET原癌基因中的突变与MEN2A、MEN2B和FMTC中的疾病表型相关后，可对RET基因发生突变的个体进行基因筛查。我们采用聚合酶链反应产物的限制性内切酶消化法替代序列分析，以快速鉴定MEN2A和FMTC呈分离状态的家族中的突变基因携带者。我们对21个澳大利亚MEN2A和FMTC家族进行了RET原癌基因富含半胱氨酸区域的突变筛查。在其中16个家族的关键个体中鉴定出7个独立突变。我们鉴定出密码子620处的一个突变，2053T→C（Cys620Arg），以及RET基因第11外显子密码子634处的两个突变，2095T→C（Cys634Arg）和2096G→A（Cys634Tyr），这三个突变均同时存在于MEN2A和FMTC家族中。
