Heutink P, van der Mey A G, Sandkuijl L A, van Gils A P, Bardoel A, Breedveld G J, van Vliet M, van Ommen G J, Cornelisse C J, Oostra B A
Department of Clinical Genetics, Academic Hospital Dijkzigt, Rotterdam, The Netherlands.
Hum Mol Genet. 1992 Apr;1(1):7-10. doi: 10.1093/hmg/1.1.7.
Paragangliomas of the head and neck are slow growing tumors which rarely show malignant progression. Familial transmission has been described consistent with an autosomal dominant mode of inheritance. Clinical manifestations of hereditary paragangliomas are determined by the sex of the transmitting parent. All affected individuals have inherited the disease gene from their father, expression of the phenotype is not observed in the offspring of an affected female until subsequent transmittance of the gene through a male carrier. This finding strongly suggests that genomic imprinting is involved. We report the results of a linkage study on a large Dutch pedigree with hereditary paragangliomas. Highly significant evidence for genetic linkage to chromosome 11q23-qter with the anonymous DNA marker D11S147 was detected with a peak lod score of 6.0 at a recombination fraction theta = 0.0. Likelihood calculations yielded an odds ratio of 2.7 x 10(6) in favor of genomic imprinting versus the absence of genomic imprinting.
头颈部副神经节瘤是生长缓慢的肿瘤，很少出现恶性进展。已经描述了家族性传递，符合常染色体显性遗传模式。遗传性副神经节瘤的临床表现由传递基因的亲本性别决定。所有受影响个体均从父亲那里继承了疾病基因，在患病女性的后代中，直到该基因通过男性携带者再次传递，才会观察到表型的表达。这一发现强烈提示涉及基因组印记。我们报告了一项对患有遗传性副神经节瘤的大型荷兰家系进行连锁研究的结果。使用匿名DNA标记D11S147检测到与11号染色体q23-qter存在高度显著的遗传连锁证据，在重组率θ = 0.0时，最高对数优势得分为6.0。似然性计算得出支持基因组印记而非无基因组印记的优势比为2.7×10(6)。
