dos Santos M R, Tanaka A, sá Miranda M C, Ribeiro M G, Maia M, Suzuki K
Instituto de Genética Médica Jacinto Magalhâes, Porto.
Am J Hum Genet. 1991 Oct;49(4):886-90.
The GM2-gangliosidosis B1 variant occurs at an exceptionally high frequency in the northern part of Portugal. In most patients, the disease manifests itself as a juvenile form, as opposed to the late-infantile form described for many patients from other parts of the world. We have analyzed the beta-hexosaminidase alpha gene in 11 patients, as well as in some relatives, in order to characterize the underlying abnormalities. They were screened for the two previously identified mutations responsible for the B1 variant phenotype (G533----A, also designated as the "DN allele," and C532---T) by PCR amplification of an 800-bp DNA fragment and subsequent dot-blot hybridization with allele-specific oligonucleotides. The fragment amplified from one patient was also subcloned and sequenced. Ten patients, constituting a clinically and biochemically homogeneous group, were found to be homozygous for the DN allele. The other, whose clinical profile more resembled the late-infantile phenotype often described in the literature, was a compound heterozygote carrying the DN allele and another, as yet unidentified, abnormal allele. Our results, corroborated by previously published data, suggest that homozygotes and compound heterozygotes for the DN allele may be distinguishable at the phenotypic level, depending on the nature of the abnormality in the other allele. A common ancestral origin for the DN allele can also be postulated.
GM2神经节苷脂沉积症B1变异型在葡萄牙北部的出现频率异常高。在大多数患者中，该疾病表现为青少年型，这与世界其他地区许多患者所描述的晚婴儿型不同。我们分析了11名患者以及一些亲属的β-己糖胺酶α基因，以确定潜在的异常情况。通过PCR扩增一个800 bp的DNA片段，随后与等位基因特异性寡核苷酸进行点杂交，对他们进行了筛查，以检测两个先前确定的导致B1变异型表型的突变（G533→A，也称为“DN等位基因”，以及C532→T）。从一名患者扩增的片段也进行了亚克隆和测序。发现10名患者在临床和生化上属于同一组，均为DN等位基因的纯合子。另一名患者的临床特征更类似于文献中经常描述的晚婴儿型表型，是携带DN等位基因和另一个尚未确定的异常等位基因的复合杂合子。我们的结果得到了先前发表数据的证实，表明DN等位基因的纯合子和复合杂合子在表型水平上可能是可区分的，这取决于另一个等位基因异常的性质。也可以假定DN等位基因有一个共同的祖先起源。
