Schollen E, Kjaergaard S, Legius E, Schwartz M, Matthijs G
Center for Human Genetics, University of Leuven, Belgium.
Eur J Hum Genet. 2000 May;8(5):367-71. doi: 10.1038/sj.ejhg.5200470.
The R141H mutation in the PMM2 gene is the most frequent mutation in type Ia of the congenital disorders of glycosylation (formerly carbohydrate-deficient glycoprotein syndromes)(CDG-Ia). However, it has never been observed in the homozygous state. Homozygosity for this mutation is probably incompatible with life. In this study, we determined the frequency of R141H in two normal populations: in neonates of Dutch origin 1/79 were carriers, whilst in the Danish population, a carrier frequency of 1/60 was found. These figures are clearly in disequilibrium with the frequency of CDG-Ia that has been estimated at 1/80,000 to 1/40,000 in these populations. Haplotype analysis of 43 patients with the R141H mutation of different geographic origins indicated that the R141H is an old mutation in the Caucasian population. Based on the new data, the disease frequency has been calculated at 1/20,000 in these populations. It is concluded that the disease is probably underdiagnosed.
磷酸甘露糖变位酶2（PMM2）基因中的R141H突变是先天性糖基化障碍Ia型（以前称为碳水化合物缺乏糖蛋白综合征，即CDG - Ia）中最常见的突变。然而，从未观察到该突变的纯合状态。这种突变的纯合性可能与生命不相容。在本研究中，我们确定了R141H在两个正常人群中的频率：在荷兰裔新生儿中，1/79为携带者，而在丹麦人群中，携带者频率为1/60。这些数字与这些人群中估计的CDG - Ia频率（1/80,000至1/40,000）明显不平衡。对43名来自不同地理区域且携带R141H突变的患者进行单倍型分析表明，R141H是白种人群中的一个古老突变。基于新数据，这些人群中的疾病频率计算为1/20,000。结论是该疾病可能未得到充分诊断。
