Spiegel R, Mächler M, Stocker H P, Boltshauser E, Schmid W
Institut für Medizinische Genetik, Universität Zürich.
Schweiz Med Wochenschr. 1991 Oct 5;121(40):1445-52.
To establish preclinical DNA-diagnosis of neurofibromatosis type 1 (NF1) in familial cases we have investigated 38 families segregating for the disease. The families were tested with 6 polymorphic DNA markers from the chromosome region 17p11.1-q11.2. Two-thirds of the families were informative for flanking markers. An informative situation was achieved for 33 out of 40 individuals at risk (i.e. first degree relatives): 30 cases were diagnosed as noncarriers of the mutated gene, and three clinically normal individuals (including an adult and two children aged three and six respectively) were found to carry the risk haplotype. The remaining 7 persons at risk could not be typed unequivocally due to non-informative markers or recombination events. In 5 families with healthy grandparents the origin of the mutation could be traced back to the grandfather's germ cells. Despite the recent cloning and initial characterization of parts of NF1 gene, studies using linked and eventually intragenic DNA markers will continue to be of great value for genetic counselling. Such analyses allow highly accurate preclinical and prenatal diagnosis in close relatives of familial cases.
为了在家族性病例中建立1型神经纤维瘤病（NF1）的临床前DNA诊断，我们研究了38个患有该疾病的家族。使用位于17号染色体区域p11.1 - q11.2的6个多态性DNA标记对这些家族进行检测。三分之二的家族对于侧翼标记具有信息性。在40名有患病风险的个体（即一级亲属）中，33人获得了信息性结果：30例被诊断为未携带突变基因，3名临床正常个体（包括1名成年人和2名分别为3岁和6岁的儿童）被发现携带风险单倍型。其余7名有患病风险的个体由于标记无信息或发生重组事件而无法明确分型。在5个祖父母健康的家族中，突变的起源可追溯到祖父的生殖细胞。尽管最近已经克隆并初步鉴定了部分NF1基因，但使用连锁以及最终的基因内DNA标记进行的研究对于遗传咨询仍将具有重要价值。此类分析能够对家族性病例的近亲进行高度准确的临床前和产前诊断。
