Goodman A B
Epidemiology and Health Services Research Laboratory, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962.
Schizophr Bull. 1994;20(3):507-17. doi: 10.1093/schbul/20.3.507.
To limit the genetic heterogeneity of schizophrenia, this study focused on the widely extended pedigrees of Ashkenazi Jewish schizophrenia probands. The hypothesis posed is that the increased prevalence among the Ashkenazim of the rare lysosomal enzyme disorders, Tay Sachs disease (TDS), caused by low levels of hexosaminidase A, and Gaucher's disease (GD), caused by low levels of glucocerebrosidase, might contribute to the demonstrated increased vulnerability to schizophrenia in this ethnic group. Signs and symptoms characterizing the candidate illnesses were systematically queried by the family history method. Rates and relative risks for symptoms characterizing these disorders and for several nonautosomal illnesses associated with TSD and/or GD (i.e., amyotrophic lateral sclerosis and Hodgkin's disease, leukemia and lymphoma) are significantly elevated in the schizophrenia pedigrees, compared to controls. The conditions with elevated rates and risks have been associated with chromosomal regions 1q21 and 15q23-q24. These areas are suggested as candidate regions for future targeted deoxyribonucleic acid (DNA) research in schizophrenia.
为限制精神分裂症的遗传异质性,本研究聚焦于德系犹太精神分裂症先证者广泛扩展的家系。提出的假设是,在德系犹太人中,由低水平的己糖胺酶A引起的罕见溶酶体酶疾病——泰-萨克斯病(TDS),以及由低水平的葡萄糖脑苷脂酶引起的戈谢病(GD)的患病率增加,可能导致该族群中已证实的对精神分裂症易感性增加。通过家族史方法系统地询问了候选疾病的体征和症状。与对照组相比,精神分裂症家系中这些疾病特征性症状以及与TDS和/或GD相关的几种非常染色体疾病(即肌萎缩侧索硬化症、霍奇金病、白血病和淋巴瘤)的发生率和相对风险显著升高。发生率和风险升高的疾病与染色体区域1q21和15q23 - q24相关。这些区域被建议作为未来精神分裂症靶向脱氧核糖核酸(DNA)研究的候选区域。