Fibrodysplasia ossificans progressiva, a heritable disorder of severe heterotopic ossification, maps to human chromosome 4q27-31
Fibrodysplasia ossificans progressiva, a heritable disorder of severe heterotopic ossification, maps to human chromosome 4q27-31
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DOI：
10.1086/302724
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发表时间：
2000-01-01
影响因子：
9.8
通讯作者：
Shore, EM
中科院分区：
文献类型：
--
作者：
Feldman, G;Li, M;Shore, EM
进行性纤维发育不良骨化症(FOP)是一种严重致残的常染色体显性结缔组织疾病，以出生后肌肉、肌腱、韧带和筋膜的进行性异位骨化和先天性足趾畸形为特征。为了确定FOP基因的染色体位置，我们进行了全基因组连锁分析，使用了四个受影响的家系，总共14个信息减数分裂。FOP表型的男性到男性传递排除了X连锁遗传。利用聚合酶链式反应扩增了覆盖所有常染色体的高度多态的微卫星标记。FOP表型与位于4q27-31区域的标记连锁(重组分数为0时LOD得分为3.10)。交叉事件将推测的FOP基因定位在36 cM的间隔内，D4S1625近端与D4S2417相邻，远端与D4S2417相邻。这个区间包含至少一个与骨形态发生蛋白信号通路有关的基因。
Fibrodysplasia ossificans progressiva (FOP) is a severely disabling, autosomal-dominant disorder of connective tissue and is characterized by postnatal progressive heterotopic ossification of muscle, tendon, ligament, and fascia and by congenital malformation of the great toes. To identify the chromosomal location of the FOP gene, we conducted a genomewide linkage analysis, using four affected families with a total of 14 informative meioses. Male-to-male transmission of the FOP phenotype excluded X-linked inheritance. Highly polymorphic microsatellite markers covering all human autosomes were amplified by use of PCR. The FOP phenotype is linked to markers located in the 4q27-31 region (LOD score 3.10 at recombination fraction 0). Crossover events localize the putative FOP gene within a 36-cM interval bordered proximally by D4S1625 and distally by D4S2417. This interval contains at least one gene involved in the bone morphogenetic protein-signaling pathway.