结节性硬化症中的基因异质性。

Genetic heterogeneity in tuberous sclerosis.

作者信息

Janssen L A, Sandkuyl L A, Merkens E C, Maat-Kievit J A, Sampson J R, Fleury P, Hennekam R C, Grosveld G C, Lindhout D, Halley D J

机构信息

Department of Clinical Genetics, Academic Hospital Dijkzigt, The Netherlands.

出版信息

Genomics. 1990 Oct;8(2):237-42. doi: 10.1016/0888-7543(90)90277-2.

DOI:10.1016/0888-7543(90)90277-2

PMID:1979047

Abstract

Tuberous sclerosis (TSC) is an autosomal dominant disorder characterized by widespread hamartosis. Preliminary evidence of linkage between the TSC locus and markers on chromosome 9q34 was established, but subsequently disputed. More recently, a putative TSC locus on chromosome 11 has been suggested and genetic heterogeneity seems likely. Here we describe an approach combining multipoint linkage analysis and heterogeneity tests that has enabled us to obtain significant evidence for locus heterogeneity after studying a relatively small number of families. Our results support a model with two different loci independently causing the disease. One locus (TSC1) maps in the vicinity of the Abelson oncogene at 9q34 and a second locus (TSC2) maps in the region of the anonymous DNA marker Lam L7 and the dopamine D2 receptor gene at 11q23.

摘要

结节性硬化症（TSC）是一种常染色体显性疾病，其特征为广泛的错构瘤病。TSC基因座与9号染色体长臂34区标记之间连锁的初步证据已经确立，但随后受到质疑。最近，有人提出11号染色体上存在一个假定的TSC基因座，而且似乎存在遗传异质性。在此，我们描述了一种结合多点连锁分析和异质性检验的方法，该方法使我们在研究了相对较少数量的家系后，获得了基因座异质性的重要证据。我们的结果支持一个由两个不同基因座独立导致该疾病的模型。一个基因座（TSC1）定位于9号染色体长臂34区的阿贝尔森癌基因附近，另一个基因座（TSC2）定位于11号染色体长臂23区匿名DNA标记Lam L7和多巴胺D2受体基因所在区域。