Williamson C, Cavaco B M, Jauch A, Dixon P H, Forbes S, Harding B, Holtgreve-Grez H, Schoell B, Pereira M C, Font A P, Loureiro M M, Sobrinho L G, Santos M A, Thakker R V
MRC Molecular Endocrinology Group, MRC Clinical Sciences Center, Imperial College School of Medicine, The Hammersmith Hospital, London, United Kingdom.
J Bone Miner Res. 1999 Feb;14(2):230-9. doi: 10.1359/jbmr.1999.14.2.230.
A Portuguese kindred with autosomal dominant isolated primary hyperparathyroidism (HPT) that was associated with parathyroid adenomas and carcinomas was investigated with the aim of determining the chromosomal location of this gene, designated HPTPort. Leukocyte DNA from 9 affected and 16 unaffected members and 7 parathyroid tumors from 4 patients was used in comparative genomic hybridization (CGH), tumor loss of heterozygosity (LOH), and family linkage studies. The CGH studies revealed abnormalities of chromosomes 1 and 13, and the results of LOH studies were consistent with the involvements of tumor suppressor genes from these regions. Family segregation studies mapped HPTPort to chromosome 1q22-q31 by establishing linkage with eight loci (D1S254, D1S222, D1S202, D1S238, D1S428, D1S2877, D1S422, and D1S412) (peak two-point LOD scores = 3. 46-5.14 at 0% recombination), and defined the location of HPT Port to a 21 cM region flanked centromerically by D1S215 and telomerically by D1S306. Thus, HPTPort has been mapped to chromosome 1q22-q31, and a characterization of this gene will help to elucidate further the mechanisms that are involved in the development of parathyroid tumors.
对一个患有常染色体显性遗传孤立性原发性甲状旁腺功能亢进症（HPT）的葡萄牙家族进行了研究，该疾病与甲状旁腺腺瘤和癌相关，目的是确定这个名为HPTPort的基因的染色体定位。来自9名患病成员、16名未患病成员的白细胞DNA以及4名患者的7个甲状旁腺肿瘤被用于比较基因组杂交（CGH）、肿瘤杂合性缺失（LOH）和家族连锁研究。CGH研究揭示了1号和13号染色体的异常，LOH研究结果与这些区域的肿瘤抑制基因的参与情况一致。家族分离研究通过与8个位点（D1S254、D1S222、D1S202、D1S238、D1S428、D1S2877、D1S422和D1S412）建立连锁，将HPTPort定位到1q22 - q31染色体（在0%重组时，两点LOD峰值分数 = 3.46 - 5.14），并将HPT Port的位置确定在一个21 cM的区域，该区域着丝粒侧由D1S215界定，端粒侧由D1S306界定。因此，HPTPort已被定位到1q22 - q31染色体，对该基因的特征描述将有助于进一步阐明甲状旁腺肿瘤发生的机制。
