SKELETAL DISORDERS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 颅骨变形不良(CMD)是一种单基因的颅管骨病，其特征是高矿化骨基质沉积在头颅和面部，而长骨则表现为膨大的干骺端骨密度降低。骨干看起来很正常。切尔鲁比症是一种过度的骨骼退化疾病，只影响上颌骨和下颌骨。过度的骨吸收首先发生在下颌骨的囊状空洞。洞中的骨头被柔软的纤维组织所取代。颌骨逐渐吸收，直到更严重的情况下只剩下皮质骨的外壳。柔软的间质组织增殖，导致特有的面部特征。孤立性先天性皮肤再生障碍性贫血(ACC)表现为先天性皮肤缺损，通常位于头皮，可缺少颅骨。毛齿骨质综合征(TDO)的患者表现为卷发、釉质发育不良和牙齿钙化不足、颅骨骨密度增加和细小的长骨管不足。 所有上述疾病都以常染色体显性遗传(AD)的方式发生，但也有零星发生，在CMD、ACC和天使症的情况下，也以常染色体隐性遗传(AR)的方式发生。阿尔茨海默病的疾病基因已经被确定。然而，有一些患者的已知疾病基因没有突变。CMD的AD形式是由ANK的突变(Reichenberger等人，2001年)、由SH3BP2的突变引起的AD切尔诺症(Ueki等人，2001年)和由DLX3的缺失引起的tdo(Price等人，1998年)。 我们的目标是识别这些基因中的其他突变，这可能有助于解释这些突变在发病过程中的作用模式。我们还试图识别和招募没有映射到已知基因座的家系，并进行全基因组筛查，特别是对于小天使症和ACC。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Craniometaphyseal dysplasia (CMD) is a monogenic craniotubular bone disorder, which is characterized by deposition of highly mineralized bone matrix in the cranium and face, whereas long bones exhibit flared metaphyses of decreased bone density. Diaphyses appear normal. Cherubism is a disorder of excessive bone degradation which affects only maxillar and mandibular bones. Excessive bone resorption occurs first in the cyst-like cavities of the mandible. Bone in the cavities is replaced by soft fibrous tissue. Jaw bones progressively resorb until in more severe cases only an outer shell of cortical bone remains. The soft stromal tissue proliferates and causes characteristic facial features. Isolated aplasia cutis congenita (ACC) manifests in congenital skin defects which are typically on the scalp, and the underlying cranial bone can be absent. Patients with trichodentoosseous syndrome (TDO) present with curled hair, enamel hypoplasia and hypocalcification of teeth, increased bone density of the skull and subtle undertubulation of long bones. All of the above disorders occur as autosomal dominant (AD) traits, but also sporadically, and in the case of CMD, ACC, and cherubism also in an autosomal recessive (AR) fashion. Disease genes for the AD form of the disorders have been identified. However, there are a number of patients who did not have mutations in the known disease genes. The AD form of CMD is caused by mutations in ANK (Reichenberger et al., 2001), AD cherubism by mutations in SH3BP2 (Ueki et al., 2001), and TDO by a deletion in DLX3 (Price et al., 1998). Our goal is to identify additional mutations in these genes which could help to explain the mode of action of the mutations during pathogenesis. We also attempt to identify and recruit families which do not map to the known loci and perform genome-wide screening, especially for cherubism and ACC.