KINDLER SYNDROME AND ACTINIC PRURIGO: MOLECULAR ANALYSIS

阳光是迄今为止对皮肤最重要的环境伤害。确定了几种遗传性光敏性综合征的分子基础，包括着色性干皮病和Rothmund-Thomson综合征，增强了我们对太阳损伤机制的理解。这项研究计划的目标是确定基因的突变导致两个剩余的未阐明的遗传性光敏性疾病-金德勒综合征和光化性pruigo。DNA可从来自巴拿马博卡斯德尔托罗的Kindler综合征患者的独特队列和来自萨斯喀彻温省、西北地区的Keewatin和马尼托巴的Norway House的AP患者的几个队列中获得。全基因组自动扫描将加快基因分型，这将在合并的DNA样本上进行。还将通过手动分析个体样本的基因型来确认结果。通过多态性位点的基因分型缩小候选区域。在最初的研究中，受影响的个体的DNA突变将与这些疾病的不同激酶进行比较。

Sunlight is by far the most important environmental insult to the skin. Determination of the molecular basis of several inheritable photosensitivity syndromes, including Xeroderma pigmentosum and Rothmund-Thomson syndrome, has enhanced our understanding of the mechanisms of sun damage. The goal of this research proposal is the identification of genes whose mutations cause two of the remaining unelucidated heritable photosensitivity disorders-Kindler syndrome and actinic pruigo. DNA is available from a unique cohort of Kindler syndrome patients from Bocas del Toro, Panama and from several cohorts of AP patients from Saskatchewan, Keewatin in the Northwest territories and Norway House, Manitoba. Genotyping will be expedited by the availability of automated genome-wide scanning, which will be done on pooled DNA samples. Results will also be confirmed by manually analyzing the genotypes of individual samples. The candidate regions will be narrowed by genotyping at polymorphic sites. Mutations in DNA from affected individuals in the initial studies will be compared with different kindreds with these diseases.