Bénichou O D, Bénichou B, Copin H, De Vernejoul M C, Van Hul W
INSERM Unit 349, Hôpital Lariboisière, Paris, France.
J Bone Miner Res. 2000 Oct;15(10):1900-4. doi: 10.1359/jbmr.2000.15.10.1900.
Type II autosomal dominant osteopetrosis (ADO II) is characterized by an increased bone mass that contrasts with the high frequency of fractures. Linkage analysis performed in an extensive Danish family recently provided evidence for the mapping of an ADO II gene to an 8.5-cM region in chromosome 1p21 between microsatellite markers D1S486 and D1S2792. We recruited, phenotyped, and haplotyped 4F catheter ADO II families including 18 affected subjects and 29 unaffected subjects in order to narrow the candidate region and to search for genetic heterogeneity. ADO II diagnosis was ascertained by the observation of vertebral end plate thickening in at least 2 patients from successive generations. Linkage studies involved five microsatellite markers (D1S486, D1S206, D1S495, D1S248, and D1S2792) spanning 1p21. Haplotype analyses of two of our families clearly excluded the tested locus. The two remaining families gave poorly informative results. These results, combined with those previously reported in two American families, suggest that chromosomal region 1p21 is most likely a minor locus for ADO II.
II型常染色体显性骨硬化症（ADO II）的特征是骨量增加，但骨折发生率却很高。最近在一个庞大的丹麦家族中进行的连锁分析为将ADO II基因定位于1号染色体1p21上微卫星标记D1S486和D1S2792之间的一个8.5厘摩区域提供了证据。我们招募了4个ADO II家族，对其进行表型分析和单倍型分析，这些家族包括18名患病个体和29名未患病个体，目的是缩小候选区域并寻找基因异质性。通过观察连续两代中至少2名患者的椎体终板增厚来确定ADO II诊断。连锁研究涉及跨越1p21的5个微卫星标记（D1S486、D1S206、D1S495、D1S248和D1S2792）。我们对其中两个家族的单倍型分析明确排除了所检测的位点。剩下的两个家族提供的信息较少。这些结果，与之前在美国两个家族中报道的结果相结合，表明1号染色体1p21区域很可能是ADO II的一个次要位点。
