Shin Y S, Gathof B S, Podskarbi T, Sommer M, Giugliani R, Gresser U
Universitäts-Kinderkrankenhaus, München, Germany.
Eur J Pediatr. 1996 May;155(5):393-7. doi: 10.1007/BF01955270.
Classical galactosaemia caused by deficiency of galactose-1-phosphate uridyltransferase (GALT) is characterized by acute symptoms of hepatocellular dysfunction, sepsis, cataracts and failure to thrive. Galactose limitation reverses these complications immediately, however, most of these children have a long-term complication of verbal dyspraxia mental retardation and ovarian failure. The GALT gene was cloned and several mutations including the common Q188R have been reported. In this study the coding region of GALT was amplified by polymerase chain reaction from genomic DNA of classical galactosaemic individuals and characterized by direct sequencing of the products. Three missense mutations were identified in three patients with a mild galactosaemic variant: (1) replacement of threonine-138 by methionine (T138M); (2) replacement of arginine by tryptophan (R259W); and (3) replacement of threonine by alanine (T350A). All three galactosaemic individuals, one girl and two boys, have varying degrees of residual GALT activity in RBC and their galactose-1-phosphate levels decreased much faster than in other galactosaemic patients. These missense mutations occur in regions that are not highly conserved domains.
The study of the molecular basis related to the phenotype variation may indeed help to prognosticate the outcome of patients with classical galactosaemia.
由1-磷酸半乳糖尿苷转移酶（GALT）缺乏引起的经典半乳糖血症的特征是肝细胞功能障碍、败血症、白内障和发育不良的急性症状。限制半乳糖可立即逆转这些并发症，然而，这些儿童中的大多数都有语言运用障碍、智力迟钝和卵巢功能衰竭的长期并发症。GALT基因已被克隆，并且已经报道了包括常见的Q188R在内的几种突变。在本研究中，通过聚合酶链反应从经典半乳糖血症个体的基因组DNA中扩增GALT的编码区，并通过对产物进行直接测序来表征。在三名患有轻度半乳糖血症变体的患者中鉴定出三个错义突变：（1）苏氨酸-138被甲硫氨酸取代（T138M）；（2）精氨酸被色氨酸取代（R259W）；以及（3）苏氨酸被丙氨酸取代（T350A）。所有三名半乳糖血症个体，一名女孩和两名男孩，红细胞中GALT活性均有不同程度的残留，且他们的1-磷酸半乳糖水平下降速度比其他半乳糖血症患者快得多。这些错义突变发生在并非高度保守结构域的区域。
对与表型变异相关的分子基础的研究确实可能有助于预测经典半乳糖血症患者的预后。
