SKELETAL DISORDERS

骨骼疾病

• 批准号: 7719109
• 负责人: ERNST J REICHENBERGER
• 金额: $ 0.31万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7719109
• 关键词: Affect; Aplasia Cutis Congenita; Bone Density; Bone Diseases; Bone Matrix; Bone Resorption; Cephalic; Characteristics; Cherubism; Computer Retrieval of Information on Scientific Projects Database; Cyst; Defect; Dental Enamel Hypoplasia; Deposition; Diaphyses; Disease; Dysplasia; Exhibits; Face; Family; Flare; Funding; Genes; Genome; Goals; Grant; Hair; Institution; Jaw; Mandible; Maps; Metaphysis; Mutation; Numbers; Pathogenesis; Patients; Proliferating; Recruitment Activity; Research; Research Personnel; Resources; Scalp structure; Screening procedure; Skin; Source; Syndrome; Tissues; Tooth structure; United States National Institutes of Health; autosomal dominant trait; bone; cranium; long bone; skeletal disorder

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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 颅骨颅截造异常发育不良（CMD）是一种单基因颅骨骨病，其特征是在颅骨和面部高度矿物质化的骨基质沉积，而长骨表现出骨密度降低的爆炸形态。 diaphyses看起来正常。天使是一种过度骨骼降解的疾病，仅影响上颌和下颌骨骼。过度的骨吸收首先发生在下颌骨的囊肿样腔中。腔中的骨骼被软纤维组织所取代。下颌骨骼逐渐吸收，直到在更严重的情况下，只有皮质骨外壳仍然存在。软基质组织增殖并引起特征性的面部特征。孤立的阳性蛋白原（ACC）表现出通常在头皮上的先天性皮肤缺陷中，并且潜在的颅骨可能不存在。毛齿齿综合征（TDO）的患者患有卷曲的头发，牙釉质发育不全和牙齿降低，头骨的骨密度增加，长骨的细微插管。 上述所有疾病都以常染色体优势（AD）特征而出现，但也偶尔出现，对于CMD，ACC和Cherubism，也以常染色体隐性（AR）方式出现。已经确定了疾病的AD形式的疾病基因。但是，有许多患者在已知疾病基因中没有突变。 CMD的AD形式是由ANK中的突变引起的（Reichenberger等，2001），SH3BP2中突变的AD Cherubism（Ueki等，2001）和DLX3中的删除（Price等，1998）。 我们的目标是确定这些基因中的其他突变，这可以有助于解释发病机理期间突变的作用方式。我们还试图识别和招募未映射到已知基因座并进行全基因组筛查的家庭，尤其是针对Cherubism和ACC。