Heritability of Oculo-Auriculo-Vertebral Spectrum

眼-耳-椎谱的遗传力

• 批准号: 6338487
• 负责人: RICHARD E WARD
• 金额: $ 3.73万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6338487
• 关键词: congenital ear disorder; congenital eye disorder; congenital skeletal disorder; disease /disorder etiology; face; family genetics; gene expression; human genetic material tag; human subject; linkage mapping; morphology; morphometry; nucleic acid quantitation /detection; orphan disease /drug; patient oriented research; phenotype; phlebotomy

We hypothesize that a minimal expression of Oculo-Auriculo-Vertebral Spectrum is a an abnormal degree of facial asymmetry. Oculo-auriculo vertebral spectrum (OAVS) is a complex and variable set of conditions including Goldenhar syndrome and Hemifacial microsomnia that share ear, eye and cervical vertebrae anomalies often expressed unilaterally. It is widely accepted that the conditions share at least a common developmental origin in disruptions of t he embryonic first and second branchial arches. The unilateral presentation of the condition together with the frequent sporadic nature of its appearance originally suggested a non-genetic or environmental origin. However, evidence has accumulated supporting a genetic component in a sizable number of cases. Thus, Rollnick and Kaye (1983) recognized clear features of OAVS in 8% of the supposed unaffected relatives of their probands or in over 40% of the families they studied. Kaye (1992) later performed segregation analysis on a large collec tion of such families and refuted the non-genetic model. In addition, several cases of chromosomal anomalies have been reported in which various components of OAVS were present. Recently, several animal models have been described which also support a genetic contribution to OAVS. We will examine fifty families in which at least one member has clinically documented OAVS. Family members will be give careful examinations for minimal signs of the condition. In addition we will conduct a quantitative assessment of facial asymmetry in which abnormal asymmetry is define statistically. We have developed and tested two unique measures of overall facial asymmetry and established normal percentiles for these measures in a previously collected sample of 1312 normal individuals. Preliminary studies of ten OAVS families have identified five in which individuals other than the proband have abnormal degrees of facial asymmetry. The collection of additional families will allow us to determine if abnorm al facial asymmetry can be an effective marker for identifying familial forms of OAVS thereby leading to more effective molecular analyses.

我们假设，眼-耳-脊椎谱的最低限度表达是面部不对称的异常程度。眼耳脊椎谱(OAVS)是一组复杂而多变的疾病，包括Goldenhar综合征和半面部微睡眠，这些疾病共享耳朵、眼睛和颈椎的异常，通常是单侧表现的。人们普遍认为，在胚胎第一和第二鳃弓的破坏方面，这些条件至少有一个共同的发育起源。这种情况的单方面表现以及其频繁出现的零星性质最初表明是非遗传或环境原因。然而，在相当数量的病例中，已经积累了支持遗传成分的证据。因此，Rollnick和Kaye(1983)在8%的前辈假定未受影响的亲属或超过40%的他们所研究的家庭中发现了OAVS的明显特征。Kaye(1992)后来对大量这样的家系进行了分离分析，并驳斥了非遗传模型。此外，还报告了几例染色体异常，其中存在OAVS的各种成分。最近，已经描述了几个动物模型，这些模型也支持OAVS的遗传贡献。我们将检查50个家庭，其中至少有一名成员有临床记录的OAVS。家庭成员将接受仔细检查，看是否有轻微的病情迹象。此外，我们还将对面部不对称进行定量评估，其中异常不对称的定义是统计的。我们开发并测试了两种独特的面部不对称性测量方法，并在之前收集的1312名正常人样本中建立了这些测量方法的正常百分位数。对10个OAVS家庭的初步研究发现，其中5个先证者以外的人面部不对称程度不正常。收集更多的家系将使我们能够确定异常面部不对称是否可以作为识别OAVS家族形式的有效标记，从而导致更有效的分子分析。