Lubinsky Mark
Wauwatosa, Wisconsin, United States.
J Pediatr Genet. 2023 Jun 12;12(3):187-192. doi: 10.1055/s-0043-1769115. eCollection 2023 Sep.
"Obvious" recessive inheritance of Tay-Sachs disease (TSD; OMIM # 272800) took over half a century to be established. Points now taken for granted were problematic, that: (1) TSD is a biological entity, not an artificial selection of concurrent findings, (2) manifestations have narrow limits, (3) it was not part of a spectrum of disorders, and can be differentiated from other conditions, (4) it will not change to another disease, (5) it is due to a single specific gene, (6) there are no secondary causes, (7) the gene has no apparent clinical effects unrelated to TSD, and (8) the gene is inherited only as a clinical recessive. To a large extent, resolution reflected biochemical understanding that took until mid-20th century, and beyond, to change how physicians viewed diseases in general. With this, biochemical carrier screening and prenatal biochemical diagnosis have become routinely available, and it is a model for carrier population screening, while gene therapy for the disease has been reported with some degree of success. Here, the history of medical ideas about TSD and its inheritance are reviewed to show how it achieved its current status as a distinct recessive disorder.
泰-萨克斯病（TSD；OMIM编号#272800）“明显的”隐性遗传经过了半个多世纪才得以确立。现在被视为理所当然的观点在当时却存在问题，即：（1）TSD是一种生物学实体，而非对同时出现的症状的人为选择；（2）症状表现范围狭窄；（3）它不属于一系列疾病的范畴，可与其他病症区分开来；（4）它不会转变为另一种疾病；（5）它由单个特定基因引起；（6）不存在继发原因；（7）该基因没有与TSD无关的明显临床效应；（8）该基因仅作为临床隐性基因遗传。在很大程度上，这一认知的转变反映了直到20世纪中叶及以后才出现的生化理解，这种理解改变了医生对一般疾病的看法。有了这一进展，生化携带者筛查和产前生化诊断已成为常规手段，它是携带者群体筛查的一个范例，同时针对该疾病的基因治疗也已取得一定程度的成功报道。在此，回顾关于TSD及其遗传的医学观念史，以展示它是如何成为一种独特的隐性疾病并达到目前地位的。
