Palmer S E, Stephens K
Department of Medicine, University of Washington School of Medicine, Seattle.
Arch Dermatol. 1993 Nov;129(11):1424-9.
The first physician to examine a patient with a genetic disorder or birth defect is usually a specialist in a field other than genetics. The presentation of certain categories of patients of particular interest to molecular genetics research may be distinct. The recognition of these patients by clinicians is fundamental to the study of genetic disorders at the DNA level.
Neurofibromatosis type 1 is a paradigm for how the study of a single genetic disease and its multiple molecular features has been facilitated by the use of various categories of patients. Other examples of interest to dermatologists, surgeons, and other specialists are discussed to demonstrate how the identification of key patients was instrumental in studies of gene localization and subsequent cloning, gene clusters or contiguous gene deletion syndromes, or mutation phenomena such as imprinting, uniparental disomy, and gonadal mosaicism. The molecular researcher has limited access to surgical specimens, and the donation of skin, tumor, and other tissues may lead to increased knowledge of new mutations in somatic mosaicism, or loss of heterozygosity of tumor suppression genes in cancer.
Guidelines are suggested to alert the physician to each of these categories of individuals with unusual presentation, as well as to recognize that the study of families with rare disorders may enable scientists to locate the responsible genes. The teamwork of clinician and molecular researcher is essential for the advancement of our understanding of DNA mechanisms in genetic disease. The ethics involved in referral of patients to molecular genetic research studies are discussed.
首位检查患有遗传疾病或出生缺陷患者的医生通常并非遗传学领域的专家。某些分子遗传学研究特别关注的特定类型患者的临床表现可能有所不同。临床医生对这些患者的识别对于在DNA水平上研究遗传疾病至关重要。
1型神经纤维瘤病是一个范例，展示了如何通过各类患者来推动对单一遗传疾病及其多种分子特征的研究。还讨论了皮肤科医生、外科医生和其他专家感兴趣的其他例子，以说明关键患者的识别在基因定位及后续克隆、基因簇或相邻基因缺失综合征研究，或诸如印记、单亲二体性和性腺镶嵌现象等突变现象研究中所起的作用。分子研究人员获取手术标本的机会有限，而皮肤、肿瘤和其他组织的捐赠可能会增加对体细胞镶嵌现象中新突变的了解，或增加对癌症中肿瘤抑制基因杂合性缺失的认识。
建议制定指导方针，提醒医生注意这些表现异常的各类个体，并认识到对罕见疾病家族的研究可能使科学家能够找到致病基因。临床医生和分子研究人员的团队合作对于增进我们对遗传疾病中DNA机制的理解至关重要。还讨论了将患者转诊至分子遗传学研究的伦理问题。
