A novel DICER1 mutation identified in a female with ovarian Sertoli-Leydig cell tumor and multinodular goiter: a case report.
A novel DICER1 mutation identified in a female with ovarian Sertoli-Leydig cell tumor and multinodular goiter: a case report.
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DOI：
10.1186/1752-1947-8-112
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发表时间：
2014-04-03
影响因子：
1
通讯作者：
Vo Hansen T
中科院分区：
文献类型：
--
作者：
Rossing M;Gerdes AM;Juul A;Rechnitzer C;Rudnicki M;Nielsen FC;Vo Hansen T
微核糖核酸加工基因 DICER1 的种系突变已被证明易导致易发生恶变的良性肿瘤亚群，包括卵巢支持-间质细胞瘤、非毒性多结节性甲状腺肿、多房性囊性肾瘤和胸膜肺母细胞瘤，这些肿瘤可能发生在儿童和年轻人中。这可能是由于种系突变携带者中Dcr-1同源物表达减少，导致微核糖核酸加工受损，并失调靶细胞的生长和分化，导致肿瘤发生风险增加。许多种系 DICER1 突变的携带者并未受到影响，但携带者体内肿瘤的发展与不同的预后相关。尽管 Dcr-1 同源综合征表型尚未完全确定，但当一名丹麦裔女孩（病例 1 患者）在 13 岁时同时出现卵巢支持间质细胞瘤和多结节性甲状腺肿时，怀疑存在 DICER1 突变。此外，家族史包括一名男性兄弟姐妹（病例2患者）也患有多结节性甲状腺肿，并在14岁时接受了半甲状腺切除术。随后对该女孩进行的 DICER1 筛查发现了外显子 21 中的两个新突变 - 一个无义突变 (c.3647C>A, p.Ser1216*) 和一个错义突变 (c.3649T>A, p.Tyr1217Asn)。这对兄弟姐妹从他们的父亲和祖父那里继承了突变，目前两人都没有症状，表明无义突变的外显率降低。对父母的分析显示，突变以顺式形式存在，使得错义突变的贡献不太显着。我们报告了一个丹麦家族中与卵巢支持-间质细胞瘤和多结节性甲状腺肿相关的新型致病性 DICER1 突变 (p.Ser1216*)。兄弟姐妹在童年时被诊断出患有多结节性甲状腺肿。临床医生在评估有或没有甲状腺疾病家族史的年轻患者的多结节性甲状腺肿时，应意识到潜在的种系 DICER1 突变。
Germ-line mutations in the micro-ribonucleic acid processing gene DICER1 have been shown to predispose to a subset of benign tumors susceptible to malignant transformation, including ovarian Sertoli-Leydig cell tumor, nontoxic multinodular goiter, multilocular cystic nephroma and pleuropulmonary blastoma, which can occur in children and young adults. This may be due to reduced Dcr-1 homolog expression in carriers of germline mutations, which causes impairment of micro-ribonucleic acid processing and deregulates the growth and differentiation of target cells, leading to an increased risk of tumorigenesis. Many carriers of germ-line DICER1 mutations remain unaffected, but development of tumors within carriers is associated with varying prognoses. Despite the Dcr-1 homolog syndrome phenotype being incompletely defined, a DICER1 mutation was suspected when a girl (case 1 patient) of Danish ethnicity presented with both an ovarian Sertoli-Leydig cell tumor and a multinodular goiter at the age of 13 years. In addition, family history included a male sibling (case 2 patient) who also had a multinodular goiter and had undergone a hemithyroidectomy at the age of 14 years. Subsequent DICER1 screening of the girl identified two novel mutations in exon 21 - a nonsense (c.3647C>A, p.Ser1216*) and a missense (c.3649T>A, p.Tyr1217Asn) mutation. The siblings had inherited the mutations from their father and paternal grandfather, which both currently were asymptomatic, indicating reduced penetrance of the nonsense mutation. Analysis of the parents revealed that the mutations were present in cis, making the contribution of the missense mutation less significant. We report a novel pathogenic DICER1 mutation (p.Ser1216*) in a Danish family associated with ovarian Sertoli-Leydig cell tumor and a multinodular goiter. A multinodular goiter was diagnosed in the siblings during childhood. Clinicians should be aware of a potential germ-line DICER1 mutation when evaluating multinodular goiter in young patients with or without a family history of thyroid diseases.