The molecular genetics of the genodermatoses: progress to date and future directions
The molecular genetics of the genodermatoses: progress to date and future directions
复制标题
遗传性皮肤病的分子遗传学：迄今为止的进展和未来的方向
DOI：
10.1046/j.1365-2133.2003.05220.x
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发表时间：
2003
影响因子：
10.3
通讯作者：
W. Mclean
中科院分区：
文献类型：
--
作者：
A. Irvine;W. Mclean
过去十年来，人类基因组图谱计划和相关基因技术的快速进步促进了多个基因的等位基因变异与特定皮肤表型的准确关联。目前，大多数更常见的遗传性皮肤病的遗传基础已被阐明。从科学角度来说，这项工作非常成功，并产生了许多新的生物学见解。这些进展虽然令人兴奋，但尚未转化为对这些疾病患者的直接益处。基因鉴定、对基因型-表型相关性的更好理解以及一些家族中意想不到的遗传机制的披露极大地帮助了遗传咨询。了解这些疾病的分子基础对于在多种情况下进行基于 DNA 的产前诊断也至关重要，并且基于 DNA 的植入前诊断已在少数情况下使用。虽然基因图谱的这一成功时期现已接近完成，但事实证明，实现下一个目标（即基于这些潜在遗传机制的知识制定治疗策略）的进展缓慢得令人沮丧。尽管与实体内脏器官相比，皮肤基因治疗更容易进入，但皮肤基因治疗面临的挑战仍然很多，并且需要克服许多技术问题，以使基因替换或基因表达修饰能够在这些疾病中发挥有用的作用。在本文中，我们全面回顾了迄今为止在基因鉴定、基因型-表型相关性、产前诊断和皮肤基因治疗方面的进展，并探讨了该领域的未来研究方向。
The Human Genome Mapping Project and allied rapid advances in genetic technology over the past decade have facilitated accurate association of allelic variations in several genes with specific skin phenotypes. Currently the genetic bases of the majority of the more common genodermatoses have been elucidated. In scientific terms this work has been extraordinarily successful and has yielded many new biological insights. These advances, although exciting, have yet to be translated into direct benefit for patients with these diseases. Genetic counselling has been greatly aided by gene identification, by the better understanding of genotype–phenotype correlation and by the disclosure of unexpected genetic mechanisms in some families. Knowledge of the molecular basis of these disorders has also been vital in enabling DNA‐based prenatal diagnosis in several conditions and DNA‐based preimplantation diagnosis has been used in a selected few. While this successful period of gene mapping is now nearing completion, progress towards the next goal, that of developing therapeutic strategies based on the knowledge of these underlying genetic mechanisms, has proven frustratingly slow. Despite the ready access to the skin compared with solid internal organs, the challenges of cutaneous gene therapy are legion and many technical issues need to be surmounted to enable gene replacement or modification of gene expression to have a useful role in these disorders. In this article we make a comprehensive review of progress to date in gene identification, genotype–phenotype correlation, prenatal diagnosis and cutaneous gene therapy, and we examine future directions for research in this field.
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DOI：
10.1073/pnas.84.24.9248
发表时间：
1987-12-01
影响因子：
11.1
作者：
BONIFAS, JM;MORLEY, BJ;EPSTEIN, EH
通讯作者：
EPSTEIN, EH
X连锁鱼鳞病纠正性基因转移模型。
影响因子：
3.5
作者：
Freiberg,RA;Choate,KA;Deng,H;Alperin,ES;Shapiro,LJ;Khavari,PA
通讯作者：
Khavari,PA
影响因子：
6.9
作者：
Vahidnezhad, Hassan;Youssefian, Leila;Uitto, Jouni
通讯作者：
Uitto, Jouni
影响因子：
9.8
作者：
Richard, G;Rouan, F;Russell, L
通讯作者：
Russell, L
影响因子：
3.5
作者：
Keith, D;Armstrong, B;Hughes, AE
通讯作者：
Hughes, AE