Hereditary hyperparathyroidism-jaw tumor syndrome: the endocrine tumor gene HRPT2 maps to chromosome 1q21-q31.
Hereditary hyperparathyroidism-jaw tumor syndrome: the endocrine tumor gene HRPT2 maps to chromosome 1q21-q31.
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DOI：
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发表时间：
1995-04
影响因子：
9.8
通讯作者：
József Szabó;Brett Heath;Virginia Hill;C. Jackson;R. Zarbo;L. Mallette;S. Chew;G. Besser;R. Thakker;V. Huff;M. Leppert;H. Heath
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作者：
József Szabó;Brett Heath;Virginia Hill;C. Jackson;R. Zarbo;L. Mallette;S. Chew;G. Besser;R. Thakker;V. Huff;M. Leppert;H. Heath
遗传性甲状旁腺功能亢进和颌骨肿瘤综合征（HPT-JT）的特点是常染色体显性遗传，复发性甲状旁腺腺瘤、下颌骨和/或上颌纤维性骨肿瘤、Wilms肿瘤和甲状旁腺癌。该综合征在临床上和遗传学上不同于其他内分泌肿瘤综合征，似乎是由内分泌肿瘤基因“HRPT2”突变引起的。我们研究了5个HPT-JT家族（59人，20人受影响）；利用基于pcr的标记，我们在排除了几个候选基因后建立了全基因组连锁搜索。在不同的重组分数（theta）上计算Lod分数，外显率为90%。我们将HRPT2定位到1号染色体的长臂上（1q21-q31）。在theta = 0.0时，标记D1S212的最大负载评分为6.10，或bb1010(6)的几率有利于连锁。在6个遗传性Wilms肿瘤家族（96人，29例患者）中，我们发现与HRPT2密切相关的1q标记没有关联（lod评分为-15.6 [D1S191]和-17.8 [D1S196], theta = .001）。对来自三个HPT-JT家族的九个成员的九个甲状旁腺瘤和一个Wilms肿瘤进行了相关位点杂合性缺失检查。甲状旁腺瘤和Wilms肿瘤显示这些DNA标记的杂合性没有损失。我们的数据证实，HRPT2是1号染色体长臂上的一个内分泌肿瘤基因，它与HPT-JT综合征有关，但与经典的遗传性Wilms肿瘤综合征无关。
The syndrome of hereditary hyperparathyroidism and jaw tumors (HPT-JT) is characterized by inheritance, in an autosomal dominant pattern, of recurrent parathyroid adenomas, fibro-osseous tumors of the mandible and/or maxilla, Wilms tumor, and parathyroid carcinoma. This syndrome is clinically and genetically distinct from other endocrine neoplasia syndromes and appears to result from mutation of an endocrine tumor gene designated "HRPT2." We studied five HPT-JT families (59 persons, 20 affected); using PCR-based markers, we instituted a genomewide linkage search after excluding several candidate genes. Lod scores were calculated at various recombination fractions (theta), penetrance 90%. We mapped HRPT2 to the long arm of chromosome 1 (1q21-q31). The maximal lod score was 6.10 at theta = .0 with marker D1S212, or > 10(6) odds in favor of linkage. In six hereditary Wilms tumor families (96 persons, 29 affected), we found no linkage to 1q markers closely linked with HRPT2 (lod scores -15.6 [D1S191] and -17.8 [D1S196], theta = .001). Nine parathyroid adenomas and one Wilms tumor from nine members of three HPT-JT families were examined for loss of heterozygosity at linked loci. The parathyroid adenomas and Wilms tumor showed no loss of heterozygosity for these DNA markers. Our data establish that HRPT2, an endocrine tumor gene on the long arm of chromosome 1, is responsible for the HPT-JT syndrome but not for the classical hereditary Wilms tumor syndrome.