Minucci Angelo, Concolino Paola, Vendittelli Francesca, Giardina Bruno, Zuppi Cecilia, Capoluongo Ettore
Laboratory of Clinical Molecular Biology Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome, Italy.
Clin Biochem. 2008 Jun;41(9):742-5. doi: 10.1016/j.clinbiochem.2007.11.009. Epub 2007 Nov 28.
: Glucose 6-phosphate dehydrogenase (G6PD) catalyzes the first committed steps in the pentose phosphate pathway: the generation of NADPH by this enzyme is essential for protection against oxidative stress. The human enzyme is in a dimer<-->tetramer equilibrium and its stability depends on NADP(+) concentration. Herein, we report a case of a symptomatic baby affected by severe deficiency of G6PD activity due to a novel de novo genetic mutation (g1465C>T) in the thirteenth exon of its gene.
: Clinical, biochemical and genetic evaluations of the affected baby and his mother were performed.
: We found the g1465C>T novel mutation, in the thirteenth exon of G6PD gene (named "G6PD Buenos Aires variant"). This g1465C>T mutation produce a P489S substitution at protein level. The P489S mutation was absent in his mother, suggesting that G6PD Buenos Aires resulted from a de novo mutation.
: The absence of mosaicism in the baby's DNA (from saliva and blood samples) suggests that a de novo mutation event may occur in the very early stages in embryogenesis or in the mother's germ cell lines.
葡萄糖-6-磷酸脱氢酶（G6PD）催化磷酸戊糖途径中的首个关键步骤：该酶生成的NADPH对于抵御氧化应激至关重要。人类该酶处于二聚体<-->四聚体平衡状态，其稳定性取决于NADP(+)浓度。在此，我们报告一例有症状婴儿，因其基因第13外显子出现新的新生基因突变（g1465C>T）而患有严重的G6PD活性缺乏症。
对患病婴儿及其母亲进行了临床、生化和基因评估。
我们在G6PD基因的第13外显子中发现了g1465C>T新突变（命名为“G6PD布宜诺斯艾利斯变异型”）。该g1465C>T突变在蛋白质水平产生P489S替代。其母亲不存在P489S突变，提示G6PD布宜诺斯艾利斯变异型源于新生突变。
婴儿DNA（来自唾液和血液样本）中不存在嵌合体，提示新生突变事件可能发生在胚胎发育的极早期或母亲的生殖细胞系中。
