Tsilchorozidou Tasoula, Vafiadou Eleni, Yovos John G, Romeo Giovani, McKay James, Lesueur Fabienne, Bonora Elena
Department of Endocrinology, Diabetes and Metabolism, AHEPA University Hospital, 54006 Thessaloniki, Greece.
Thyroid. 2005 Dec;15(12):1349-54. doi: 10.1089/thy.2005.15.1349.
The familial form of nonmedullary thyroid carcinoma (FNMTC) has been recognized as a distinct clinical entity and is characterized by multifocality and a more severe phenotype than its sporadic counterpart. The majority of FNMTC pedigrees are small in size, show variable modes of inheritance, and may present with a variety of additional benign thyroid disorders. The existence of marked phenotypic differences between FNMTC families suggests that there is genetic heterogeneity. Recent studies have mapped a susceptibility locus for FNMTC at 2q21. This locus appears particular relevant to families with at least one case of the follicular variant of papillary thyroid cancer (fvPTC). We describe the clinical and pathologic characteristics of a large three-generation fPTC kindred, with two of the four PTC patients presented with the follicular variant of PTC. It is of interest the occurrence of PTC in three siblings within a period of 3 years. In addition, multinodular goiter (MNG) was diagnosed in seven individuals, lymphocytic thyroiditis in four, while one diagnosed with a benign adenoma. From the PTC patients, one had MNG and fvPTC, one MNG, lymphocytic thyroiditis and papillary pattern of PTC, one lymphocytic thyroiditis and fvPTC, and one MNG and papillary pattern of PTC. The inheritance pattern was autosomal dominant with incomplete penetrance and women were affected more frequently than men. Considering all PTC-affected individuals, the limit of detection (LOD) score we got for this family on 2q21 was 0.5. The low LOD score is caused by a PTC patient who does not share the affected haplotype, suggesting that maybe a new locus for PTC predisposition is present in this kindred. Linkage analysis also excluded TCO, MNG, and fPTC/PRN as susceptibility loci to FNMTC in this family.
家族性非髓样甲状腺癌（FNMTC）已被确认为一种独特的临床实体，其特征是多灶性，且表型比散发性非髓样甲状腺癌更严重。大多数FNMTC家系规模较小，显示出可变的遗传模式，并且可能伴有多种其他良性甲状腺疾病。FNMTC家系之间存在明显的表型差异，这表明存在遗传异质性。最近的研究已将FNMTC的一个易感基因座定位到2q21。该基因座似乎与至少有一例甲状腺乳头状癌滤泡变体（fvPTC）的家系特别相关。我们描述了一个大型三代甲状腺乳头状癌家系的临床和病理特征，四名甲状腺乳头状癌患者中有两名表现为PTC的滤泡变体。有趣的是，在3年内三名兄弟姐妹都发生了PTC。此外，七人被诊断为多结节性甲状腺肿（MNG），四人患有淋巴细胞性甲状腺炎，一人被诊断为良性腺瘤。在甲状腺乳头状癌患者中，一人患有MNG和fvPTC，一人患有MNG、淋巴细胞性甲状腺炎和PTC乳头状模式，一人患有淋巴细胞性甲状腺炎和fvPTC，一人患有MNG和PTC乳头状模式。遗传模式为常染色体显性遗传，具有不完全外显率，女性比男性更易受影响。考虑到所有受甲状腺乳头状癌影响的个体，我们在2q21上为这个家系获得的检测限（LOD）分数为0.5。低LOD分数是由一名不共享受影响单倍型的PTC患者导致的，这表明这个家系中可能存在一个新的PTC易感基因座。连锁分析也排除了TCO、MNG和fPTC/PRN作为该家系中FNMTC的易感基因座。
