White K E, Koller D L, Takacs I, Buckwalter K A, Foroud T, Econs M J
Department of Medicine, Indiana University School of Medicine, Indianapolis 46202, USA.
J Clin Endocrinol Metab. 1999 Mar;84(3):1047-51. doi: 10.1210/jcem.84.3.5578.
Autosomal dominant osteopetrosis (ADO), is a heritable disorder that results from a failure of osteoclast-mediated bone resorption. The etiology of the disorder is unknown. A previous linkage study of one Danish family mapped an ADO locus to chromosome 1p21. We have studied two families from Indiana with ADO. The present study sought to determine if the ADO gene in these families was also linked to chromosome 1p21. We used six microsatellite repeat markers, which demonstrated linkage to the 1p21 ADO locus in the Danish study, to perform linkage analysis in the new kindreds. Multipoint analysis excluded linkage of ADO to chromosome 1p21 (logarithm of the odds score < -7.00) in both families. In addition, no haplotype segregated with the disorder in either family. In summary, the present investigation ruled out linkage of ADO to chromosome 1p21 in two families from Indiana. Our results demonstrate that there is locus heterogeneity of this disorder; therefore, mutations in at least two different genes can give rise to the ADO phenotype.
常染色体显性遗传性骨硬化症（ADO）是一种由于破骨细胞介导的骨吸收功能障碍导致的遗传性疾病。该疾病的病因尚不清楚。先前对一个丹麦家庭的连锁研究将一个ADO基因座定位于1号染色体的1p21区域。我们研究了来自印第安纳州的两个患有ADO的家庭。本研究旨在确定这些家庭中的ADO基因是否也与1号染色体的1p21区域连锁。我们使用了六个微卫星重复标记（在丹麦的研究中这些标记显示与1p21的ADO基因座连锁），在新的家族中进行连锁分析。多点分析排除了两个家庭中ADO与1号染色体1p21区域的连锁关系（优势对数得分< -7.00）。此外，在任何一个家庭中，都没有单倍型与该疾病共分离。总之，本研究排除了印第安纳州两个家庭中ADO与1号染色体1p21区域的连锁关系。我们的结果表明，这种疾病存在基因座异质性；因此，至少两个不同基因的突变可导致ADO表型。
