Nosology and classification of genetic skeletal disorders: 2006 revision
Nosology and classification of genetic skeletal disorders: 2006 revision
复制标题
DOI：
10.1002/ajmg.a.31483
复制
发表时间：
2007-01-01
影响因子：
2
通讯作者：
Unger, Sheila
中科院分区：
文献类型：
--
作者：
Superti-Furga, Andrea;Unger, Sheila
本文的目的是提供对骨的体质障碍病因学的修订，包括新认识的疾病，并反映新的分子和致病概念。纳入疾病的标准是(1)与骨骼发育不良、代谢性骨疾病、骨骼发育不良和/或骨骼畸形和/或还原综合征的定义相对应的严重骨骼受累，(2)发表和/或微型清单，(3)遗传、基础证明或很可能的，以及(4)通过分子或连锁分析和/或多个个人或家庭的独特诊断特征和观察证实的病因学自主性。纳入372种不同的条件，并按分子、生化和/或放射学标准将其分为37组。在这些疾病中，215个与140个不同基因中的一个或多个有关。病原学状态分为最终(突变或基因定位)、可能(系谱证据)或善意(多项观察和明确的诊断标准，但尚无系谱或基因座证据)。公认的具有重要骨骼成分的遗传病的数量正在增加，发育不良、代谢性骨病、骨骼发育不良和畸形综合征之间的区别正在变得模糊。为了分类的目的，病原学和分子标准与形态标准相结合，但疾病仍然通过临床特征和放射学表现来识别。分子证据导致对单个实体的确认和新群体的组成，但也允许描绘相关但不同的实体，并表明分子机制先前意想不到的异质性；因此，分子证据不一定简化病因学，预计实体数量和复杂性将进一步增加。通过提供已确认的与骨骼有关的疾病和潜在基因缺陷的最新概述，新的病因学呼吁提供实际的诊断帮助，促进新实体的识别，并促进和指导骨骼生物学和遗传疾病的研究。(C)2006年Wiley-Liss，Inc.
The objective of the paper is to provide the revision of the Nosology of Constitutional Disorders of Bone that incorporates newly recognized disorders and reflects new molecular and pathogenetic concepts. Criteria for inclusion of disorders were (1) significant skeletal involvement corresponding to the definition of skeletal dysplasias, metabolic bone disorders, dysostoses, and skeletal malformation and/or reduction syndromes, (2) publication and/or MINI listing, (3) genetic, basis proven or very likely, and (4) nosologic autonomy confirmed by molecular or linkage analysis and/or distinctive diagnostic features and observation in multiple individuals or families. Three hundred seventy-two different conditions were included and placed in 37 groups defined by molecular, biochemical and/or radiographic criteria. Of these conditions, 215 were associated with one or more of 140 different genes. Nosologic status was classified as final (mututions or locus identified), probable (pedigree evidence), or bona fide (multiple observations and clear diagnostic criteria, but no pedigree or locus evidence yet). The number of recognized genetic disorders with a significant skeletal component is growing and the distinction between dysplasias, metabolic bone disorders, dysostoses, and malformation syndromes is blurring. For classification purposes, pathogentic and molecular criteria are integrating with morphological ones but disorders are still identified by clinical features and radiographic appearance. Molecular evidence leads to confirmation of individual entities and to the constitution of new groups, but also allows for delineation of related but distinct entities and indicates a previously unexpected heterogeneity of molecular mechanisms; thus, molecular evidence does not necessarily simplify the Nosology, and a further increase in the number of entities and growing complexity is expected. By providing an updated overview of recognized with skeletal involvement and of the underlying gene defects, the new Nosology call provide practical diagnostic help, facilitate the recognition of new entities, and foster and direct research in skeletal biology and genetic disorders. (c) 2006 Wiley-Liss, Inc.