An integrative approach for the diagnosis, characterization and prevention of autosomal recessive congenital ichthyosis in the Middle East

常染色体隐性遗传性先天性鱼鳞病(ARCI)以皮肤普遍鳞屑和变异性红斑为特征。它表现出广泛的临床和遗传异质性。目前已知有五个ARCI基因座和两个类似表型的基因座，到目前为止，已鉴定出五个基因的突变，分别属于其中四个基因座。其他潜在的基因仍然未知，甚至必须存在更多的ARCI基因座。由于近亲结婚率很高，中东地区ARCI的发病率明显较高。因此，我们打算以一种全面的方法从中东招募ARCI患者家庭，并从临床和分子特征上确定该地区的疾病特征。这将导致快速和相当便宜的标准化诊断方案，这些方案可以转移到当地医疗中心，并是进一步研究中东鱼鳞病遗传流行病学的先决条件。未被分配到ARCI已知基因之一的近亲家族将特别有助于通过纯合作图来识别和提炼新的基因座。因此，这种综合的方法将开发出大量的医学工具，并对更好地了解表皮的生理过程和角质形成细胞的分化具有广泛的影响。

Autosomal recessive congenital ichthyosis (ARCI) is characterized by generalized scaling of the skin and variable erythema. It presents extensive clinical and genetic heterogeneity. Five loci for ARCI and two loci for similar phenotypes are known today, and mutations in five genes, assigned to four of the loci, were identified so far. The other underlying genes are still unknown, and even further loci for ARCI must exist. Because of the high rate of consanguineous marriages, there is a significantly higher incidence of ARCI in the Middle East. Therefore we intend to recruit families with ARCI from the Middle East in a comprehensive approach and clinically and molecularly characterize the disease in the region. This will result in fast and rather inexpensive standardized diagnostic schemes, which can be transferred to local medical centers and are a prerequisite for further genetic epidemiologic studies of ichthyosis in the Middle East. Consanguineous families not assigned to one of the known genes for ARCI will be particularly useful for identifying and refining novel loci by homozygosity mapping. Hence the integrative approach will both develop substantial medical tools and be of wide impact to better understanding physiological processes of the epidermis and the differentiation of keratinocytes.