Clinical and ATP7A gene analysis of three infants with Menkes disease and prenatal diagnosis for a fetus at risk

Menkes病是一种罕见的X连锁隐性遗传病，由于ATP7A基因突变导致铜吸收障碍，铜相关酶功能缺陷，引起多系统功能障碍。该文拟通过对3例Menkes病患儿的临床经过和ATP7A基因突变分析对该症进行研究，并对1例再孕母亲进行产前诊断研究。3例男婴于8~9个月时来院就诊，均为婴儿期起病，主要表现为抽搐和智力运动落后，抗癫癎治疗无效，面色苍白，毛发稀疏、卷曲，小头，MRI扫描显示脑萎缩、白质异常、基底节损害和脑血管形态改变，血浆铜蓝蛋白均显著降低，分别为70.2、73.5、81.0 mg/L（参考值210~530 mg/L），符合经典型Menkes病临床表型。例1和2的ATP7A基因存在c.3914A>G（p. D1305G）突变，例3为c.3265G>T（p.G1089X）突变，均为新生突变。c.3914A>G（p. D1305G）为已知突变，c.3265G>T（p.G1089X）为新突变，均为我国首次报道。例1患儿的母亲再孕，于妊娠20周时抽取羊水细胞，通过胎儿ATP7A基因突变分析，进行产前诊断。羊水细胞ATP7A基因未见c.3914A>G，提示胎儿未患与先证者相同的疾病。胎儿出生后发育正常。Menkes disease is a rare X-linked recessive disorder characterized by multi-systemic disorder of copper deifciency caused by ATP7A gene mutation. In this study, the clinical and laboratory features of three patients with Menkes disease were analyzed. Prenatal diagnosis had been performed for a fetus of a family. Three patients were admitted at the age of 8-9 months due to severe epilepsies and marked delayed psychomotor development. Signiifcantly light complexion, pudgy cheeks and sparse fuzzy wooly hair were observed. On their cranial MR imaging, cortical atrophy, leukoencephalopathy, basal ganglia damage and tormesity of the intracranial vessels were found. Their plasma ceruloplasmin decreased to 70.2, 73.5 and 81 mg/L, signiifcantly lower than normal range (210-530 mg/L). c.3914A>G (p. D1305G) was detected on ATP7A gene of case 1 and 2. A novel mutation, c.3265G>T (p.G1089X) was found in case 3. Both of them were ifrstly found in Chinese patients of Menkes disease. The mother of case 1 was tested at 20 weeks of pregnancy. Karyotype and ATP7A gene studies of the amniocytes were performed for the prenatal diagnosis of her fetus. Normal male karyotypes without c.3914A>G mutation on ATP7A gene was showed. Postnatal genetic analysis and normal development conifrmed the prenatal diagnosis.“十二五”国家科技支撑计划项目(2012BAI09B04)资助。PubMed中文核心期刊要目总览(PKU)中国科技核心期刊(ISTIC)中国科学引文数据库(CSCD)06624-6281