Ashworth A, Abusaad I, Walsh C, Nanko S, Murray R M, Asherson P, McGuffin P, Gill M, Owen M J, Collier D A
Institute of Psychiatry, Department of Psychological Medicine, London, UK.
Psychiatr Genet. 1996 Summer;6(2):81-6. doi: 10.1097/00041444-199622000-00008.
We have examined 23 families multiply affected with schizophrenia for linkage to the FMR-1 gene on the X chromosome. Alleles at the FMR-1 CGG triplet repeat were analysed by the polymerase chain reaction, and methylation status at the FMR-1 locus in individuals with evidence of expanded or unstable repeats was analysed by Southern hybridization. Two-point LOD score analyses with a range of X-linked single gene models and a non-parametric affected sib-pair method revealed no evidence for linkage. In one family, however, a fragile X premutation was found, and one individual with schizophrenia and developmental delay was a mosaic for the full and premutation. We conclude that although mutations within the FMR-1 gene do not have a major aetiological role in schizophrenia in our collection of pedigrees, it is possible that FMR-1 mutations can modify the clinical phenotype of schizophrenia.
我们研究了23个精神分裂症多发家系，以确定其与X染色体上FMR-1基因的连锁关系。采用聚合酶链反应分析FMR-1基因CGG三联体重复序列的等位基因，并通过Southern杂交分析有重复序列扩增或不稳定证据个体的FMR-1基因座甲基化状态。采用一系列X连锁单基因模型和非参数患病同胞对法进行两点LOD评分分析，未发现连锁证据。然而，在一个家系中发现了一个脆性X前突变，一名患有精神分裂症和发育迟缓的个体为全突变和前突变的嵌合体。我们得出结论，虽然在我们收集的家系中，FMR-1基因突变在精神分裂症中没有主要病因学作用，但FMR-1基因突变有可能改变精神分裂症的临床表型。
