Teh B T, Farnebo F, Kristoffersson U, Sundelin B, Cardinal J, Axelson R, Yap A, Epstein M, Heath H, Cameron D, Larsson C
Department of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.
J Clin Endocrinol Metab. 1996 Dec;81(12):4204-11. doi: 10.1210/jcem.81.12.8954016.
Hereditary hyperparathyroidism-jaw tumor syndrome (HPT-JT) is an autosomal dominant disease (OMIM 145001) that has recently been mapped to chromosomal region 1q21-q32 (HRPT2). Here we report two families with HPT-JT syndrome in which adult renal hamartomas or cystic kidney disease were prominent associated features, possibly representing a new phenotypic variant of the HPT-JT syndrome. In the first family, renal lesions were present in five out of six affected individuals, whereas HPT and JT were seen in four and two cases, respectively. In the second family, JT was found in three of the five affected individuals and two affected members also exhibited polycystic kidney disease. The possibility of the latter cosegregating as a separate autosomal dominant gene can not be ruled out. A sex-dependent penetrance of primary HPT, resulting in predominantly male-affected cases was evident in the two families. Twenty microsatellite markers in the HRPT2 region were typed, in addition to markers in the multiple endocrine neoplasia (MEN) types 1 and 2 regions at 11q13 and 10q11. The disease in these two kindreds was linked to five markers in the 1q21-q32 region (logarithm-of-odds scores: 3.2-4.2), whereas linkage to the MEN1 and MEN2 regions was excluded. Meiotic recombinations detected in affected individuals placed the locus telomeric of D1S215, thus narrowing the HRPT2 region from > 60 to approximately 34 centimorgans. Loss of heterozygosity was studied in seven renal hamartomas from two affected individuals in the first family, as well as in a jaw tumor and a parathyroid tumor from the second family. All renal hamartomas showed loss of heterozygosity at the 1q21-q32 region. The losses invariably involved the wild type allele derived from the unaffected parent, suggesting the inactivation of a tumor suppressor gene in this region.
遗传性甲状旁腺功能亢进-颌骨肿瘤综合征（HPT-JT）是一种常染色体显性疾病（OMIM 145001），最近已被定位到染色体区域1q21-q32（HRPT2）。在此，我们报告两个患有HPT-JT综合征的家系，其中成人肾错构瘤或多囊肾病是突出的相关特征，可能代表HPT-JT综合征的一种新的表型变异。在第一个家系中，6名受影响个体中有5人存在肾脏病变，而分别有4例和2例出现甲状旁腺功能亢进和颌骨肿瘤。在第二个家系中，5名受影响个体中有3人出现颌骨肿瘤，2名受影响成员还表现出多囊肾病。不能排除后者作为一个单独的常染色体显性基因共分离。在这两个家系中，原发性甲状旁腺功能亢进存在性别依赖性外显率，导致主要是男性受影响。除了位于11q13和10q11的多内分泌腺瘤（MEN）1型和2型区域的标记外，还对HRPT-2区域的20个微卫星标记进行了分型。这两个家系中的疾病与1q21-q32区域的5个标记连锁（优势对数分数：3.2-4.2），而与MEN1和MEN2区域的连锁被排除。在受影响个体中检测到的减数分裂重组将该基因座定位到D1S215的端粒，从而将HRPT2区域从大于60厘摩缩小到约34厘摩。对第一个家系中两名受影响个体的7个肾错构瘤以及第二个家系中的一个颌骨肿瘤和一个甲状旁腺肿瘤进行了杂合性缺失研究。所有肾错构瘤在1q21-q32区域均显示杂合性缺失。这些缺失总是涉及来自未受影响亲本的野生型等位基因，表明该区域的一个肿瘤抑制基因失活。
