SKELETAL DISORDERS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 颅后骺端发育不良（CMD）是一种单基因颅管状骨疾病，其特征是在颅骨和面部沉积高度矿化的骨基质，而长骨表现出骨密度降低的外展干骺端。骨干看起来正常。巨颌症是一种骨质过度退化的疾病，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肿样腔中。空腔中的骨被软纤维组织所取代。颌骨逐渐再吸收，直到在更严重的情况下，只剩下皮质骨的外壳。软基质组织增生并导致面部特征。孤立性先天性皮肤发育不全（ACC）表现为先天性皮肤缺损，通常在头皮上，并且下面的颅骨可以缺失。牙骨质疏松综合征（TDO）患者表现为头发卷曲、牙釉质发育不全和钙化不全、颅骨骨密度增加和长骨轻微的骨质疏松。 所有上述疾病都以常染色体显性（AD）性状发生，但也偶尔发生，并且在CMD、ACC和巨像症的情况下也以常染色体隐性（AR）方式发生。已经鉴定了AD形式的疾病的疾病基因。然而，有一些患者在已知的疾病基因中没有突变。 AD形式的CMD由ANK突变引起（Reichenberger et al.，2001）、SH 3BP 2突变引起的AD巨像症（Ueki等人，2001）和通过DLX 3中的缺失的TDO（Price et al.，1998年）。 我们的目标是确定这些基因中的其他突变，这可能有助于解释发病过程中突变的作用模式。我们还试图确定和招募家庭不映射到已知的基因座，并进行全基因组筛选，特别是对cherubism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.