Yoshimoto K, Endo H, Tsuyuguchi M, Tanaka C, Kimura T, Iwahana H, Kato G, Sano T, Itakura M
Otsuka Department of Clinical and Molecular Nutrition, School of Medicine, University of Tokushima, Japan.
Clin Endocrinol (Oxf). 1998 Jan;48(1):67-72. doi: 10.1046/j.1365-2265.1998.00354.x.
Familial isolated primary hyperparathyroidism (FIHP) is a rare hereditary disorder. We present four patients from a single family with FIHP, and genetic analysis of their parathyroid adenomas and parathyroid carcinoma.
DNA was extracted from tumours resected at surgery. Tumours were examined for loss of heterozygosity (LOH) with microsatellite polymorphic markers.
The 27-year-old proband (Patient 1) died of parathyroid carcinoma with metastases to the lungs and chest wall. Sixteen years later, his 34-year-old sister (Patient 2) presented with a neck tumour and primary hyperparathyroidism. Family screening revealed parathyroid tumours in his 36-year-old sister (Patient 3) and 29-year-old cousin (Patient 4). Histological examination of resected tumours showed parathyroid carcinoma and adenoma in Patient 2, a parathyroid adenoma in Patient 3, and an atypical parathyroid adenoma in Patient 4. Autopsy of the proband ruled out multiple endocrine neoplasia (MEN) type 1, and the three patients who underwent parathyroidectomy did not exhibit any abnormalities in the pancreas or the pituitary gland.
Analysis of tumour DNA from one parathyroid carcinoma (Patient 2), the atypical parathyroid adenoma (Patient 4), and two parathyroid adenomas (Patients 2 and 3) showed limited LOH on chromosomes 13q12.3-q32 in an adenoma of Patient 2 and 9p21-p22 and 13q12.3-q32 in an adenoma of Patient 3.
These results suggest the possible contribution of tumour suppressor genes including the retinoblastoma gene and the hereditary breast cancer susceptibility gene (BRCA2) on 13q to parathyroid tumours in this family.
家族性孤立性原发性甲状旁腺功能亢进症（FIHP）是一种罕见的遗传性疾病。我们报告了来自同一个家族的4例FIHP患者，并对他们的甲状旁腺腺瘤和甲状旁腺癌进行了基因分析。
从手术切除的肿瘤中提取DNA。使用微卫星多态性标记检查肿瘤的杂合性缺失（LOH）。
27岁的先证者（患者1）死于伴有肺和胸壁转移的甲状旁腺癌。16年后，他34岁的姐姐（患者2）出现颈部肿瘤和原发性甲状旁腺功能亢进症。家族筛查发现他36岁的姐姐（患者3）和29岁的表弟（患者4）患有甲状旁腺肿瘤。对切除肿瘤的组织学检查显示，患者2为甲状旁腺癌和腺瘤，患者3为甲状旁腺腺瘤，患者4为非典型甲状旁腺腺瘤。对先证者的尸检排除了1型多发性内分泌肿瘤（MEN），接受甲状旁腺切除术的3例患者在胰腺或垂体未发现任何异常。
对1例甲状旁腺癌（患者2）、1例非典型甲状旁腺腺瘤（患者4）和2例甲状旁腺腺瘤（患者2和3）的肿瘤DNA分析显示，患者2的1例腺瘤在染色体13q12.3-q32存在有限的杂合性缺失，患者3的1例腺瘤在9p21-p22和13q12.3-q32存在杂合性缺失。
这些结果表明，包括13q上的视网膜母细胞瘤基因和遗传性乳腺癌易感基因（BRCA2）在内的肿瘤抑制基因可能与该家族的甲状旁腺肿瘤有关。
