Au Wing-Yan, Lam Veronica, Pang Annie, Lee Wing-Man, Chan Jess L C, Song You-Qiang, Ma Edmond S, Kwong Yok-Lam
Department of Medicine, Professorial Block, Queen Mary Hospital, Pokfulam Road, Hong Kong.
J Gerontol A Biol Sci Med Sci. 2006 Oct;61(10):1086-9. doi: 10.1093/gerona/61.10.1086.
Age-related skewing of X-chromosome inactivation leading to glucose-6-phosphate dehydrogenase (G6PD) deficiency in elderly women in a population with prevalent G6PD gene mutations was investigated.
G6PD activity was measured biochemically. G6PD mutations were detected by polymerase chain reaction (PCR) and allele-specific extension, and analyzed by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry and Sequenom MassARRAY. X-chromosome inactivation was quantified by semiquantitative PCR for the HUMARA gene, before and after HpaII digestion.
In 173 women (median age: 90 years; range, 80-107 years), 18 heterozygotes for G6PD mutations were identified. Three heterozygotes were G6PD deficient, owing to skewed X-chromosome inactivation affecting the wild-type allele. Fifteen heterozygotes, with skewing apparently affecting the mutant alleles, had normal but significantly lower G6PD levels. At 1.73%, G6PD deficiency was significantly more frequent than expected from population screening at birth.
Due to skewed X-chromosome inactivation, elderly women in populations with prevalent G6PD mutations are at risk of G6PD deficiency.
在一个葡萄糖-6-磷酸脱氢酶（G6PD）基因突变普遍存在的人群中，研究了与年龄相关的X染色体失活偏斜导致老年女性G6PD缺乏症的情况。
采用生化方法测定G6PD活性。通过聚合酶链反应（PCR）和等位基因特异性延伸检测G6PD突变，并通过基质辅助激光解吸电离飞行时间（MALDI-TOF）质谱和Sequenom MassARRAY进行分析。在HpaII消化前后，通过对HUMARA基因进行半定量PCR来量化X染色体失活。
在173名女性（中位年龄：90岁；范围80 - 107岁）中，鉴定出18名G6PD突变杂合子。由于影响野生型等位基因的X染色体失活偏斜，3名杂合子G6PD缺乏。15名杂合子的X染色体失活偏斜显然影响了突变等位基因，其G6PD水平正常但显著较低。G6PD缺乏症的发生率为1.73%，明显高于出生时人群筛查的预期发生率。
由于X染色体失活偏斜，在G6PD突变普遍存在的人群中，老年女性有患G6PD缺乏症的风险。
