3 例Menkes病患儿的临床与ATP7A基因分析及1例产前诊断研究

王峤; 丁圆; 王静敏; 黄琼辉; 赵程峰; 刘玉鹏; 李溪远; 吴桐菲; 宋金青; 王玉洁; 杨艳玲

doi:10.7499/j.issn.1008-8830.2014.06.013

PDF(1309 KB)

HTML

中国当代儿科杂志 ›› 2014, Vol. 16 ›› Issue (6) : 624-628. DOI: 10.7499/j.issn.1008-8830.2014.06.013

论著·临床研究

3 例Menkes病患儿的临床与ATP7A基因分析及1例产前诊断研究

王峤, 丁圆, 王静敏, 黄琼辉, 赵程峰, 刘玉鹏, 李溪远, 吴桐菲, 宋金青, 王玉洁, 杨艳玲

作者信息 +

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

WANG Qiao, DING Yuan, WANG Jing-Min, HUANG Qiong-Hui, ZHAO Cheng-Feng, LIU Yu-Peng, LI Xi-Yuan, WU Tong-Fei, SONG Jin-Qing, WANG Yu-Jie, YANG Yan-Ling

Author information +

Department of Pediatrics, Peking University First Hospital, Beijing 100034, China

Aboat authors:

[1] Menkes JH, Alter M, Steigleder GK, et al. A sex-linked recessive disorder with retardation of growth, peculiar hair and focal cerebral and cerebellar degeneration[J].Pediatrics, 1962, 29 (5): 764-779.
[2] Gu YH, Kodama H, Shiga K, et al. A survey of Japanese patients with Menkes disease from 1990 to 2003: incidence and early signs before typical symptomatic onset, pointing the way to earlier diagnosis[J].J Inherit Metab Dis, 2005, 28 (4): 473-478.
[3] 王晓慧, 吕俊兰, 张礼萍, 等. Menkes 病三例临床及实验室特点[J].中华儿科杂志, 2009, 47 (8): 604-606.
[4] 赵程峰, 王静敏, 王菊莉, 等. Menkes 病患儿ATP7A 基因突变及X 染色体失活分析[J].中国伤残医学, 2013, 21 (5): 37-41.
[5] 麻宏伟, 陈丽英, 张海娟, 等. Menkes 病一家系二例[J].中华医学遗传学杂志, 2001, 18 (4): 258.
[6] Kaler SG. Diagnosis and therapy of Menkes syndrome, a genetic form of copper deficiency[J].Am J Clin Nutr, 1998, 67 (5): 1029- 1034.
[7] Tümer Z. An Overview and update of ATP7A mutations leading to menkes disease and occipital horn syndrome[J].Hum Mutat, 2013, 34 (3): 417-429.
[8] Christodoulou J, Danks DM, Sarkar B, et al. Early treatment of Menkes disease with parenteral copper-histidine: long-term follow-up of four treated patients[J].Am J Med Genet, 1998, 76 (2): 154-164.
[9] Gourdon P, Liu XY, Skjorringe T, et al. Crystal structure of a copper-transporting PIB-type ATPase[J].Nature, 2011, 475 (7354): 59-64.
[10] Lutsenko S, LeShane ES, Shinde U. Biochemical basis of regulation of human coppertransporting ATPases[J].Arch Biochem Biophys, 2007, 463(2): 134-148.
[11] Palmgren MG, Nissen P. P-type ATPases[J].Annu Rev Biophys, 2011, 40: 243-266.
[12] Horn N, Tümer Z. Menkes disease and the occipital horn syndrome[M]// Royce PM, Steinmann B. Connecitive Tissue and its Heritable Disorders: Molecular, Genetic, and Medical Aspects. 2nd ed. New York: John Wiley and Sons Inc, 2002: 651-685.
[13] 黄琼辉, 王静敏, 吴晔, 等. Menkes 病临床及ATP7A 基因突变和拷贝数改变分析[J].实用儿科临床杂志, 2012, 27 (8): 570-573.
[14] 邓艳华, 王静敏, 牛争平, 等. Menkes 病患儿ATP7A 基因突变分析[J].实用儿科临床杂志, 2007, 22 (24): 1877-1879.
[15] 程晓悦, 肖江喜, 袁新宇, 等. Menkes 病的MR 影像表现[J].中华放射学杂志, 2013, 47 (7): 599-602.
[16] Tümer Z, Vural B, Tunnesen T, et al. Characterization of the exon structure of the Menkes disease gene using vectorette PCR[J].Genomics, 1995, 26 (3): 437-442.
[17] Tümer Z, Tunnesen T, Bohmann J, et al. First trimester prenatal diagnosis of Menkes disease by DNA analysis[J].J Med Genet, 1994, 31 (8): 615-617.
[18] Horn N. Menkes' X-linked disease: prenatal diagnosis and carrier detection[J].J Inherit Metab Dis, 1983, 6(1): 59-62.
[19] Heydorn K, Damsgaard E, Horn N. Accumulated experience with prenatal diagnosis of Menkes disease by neutron activation analysis of chorionic villi specimens[J].Biol Trace Elem Res, 1999, 71-72; 551-561.
[20] Das S, Whitney S, Taylor J, et al. Prenatal diagnosis of Menkes disease by mutation analysis[J].J Inher Metab Dis, 1995, 18 (3): 364-365.

Show less

文章历史 +

摘要

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。

Abstract

Menkes disease is a rare X-linked recessive disorder characterized by multi-systemic disorder of copper deficiency 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. Significantly 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, significantly 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 firstly 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 confirmed the prenatal diagnosis.

导出引用

王峤, 丁圆, 王静敏, 黄琼辉, 赵程峰, 刘玉鹏, 李溪远, 吴桐菲, 宋金青, 王玉洁, 杨艳玲. 3 例Menkes病患儿的临床与ATP7A基因分析及1例产前诊断研究[J]. 中国当代儿科杂志. 2014, 16(6): 624-628 https://doi.org/10.7499/j.issn.1008-8830.2014.06.013

WANG Qiao, DING Yuan, WANG Jing-Min, HUANG Qiong-Hui, ZHAO Cheng-Feng, LIU Yu-Peng, LI Xi-Yuan, WU Tong-Fei, SONG Jin-Qing, WANG Yu-Jie, YANG Yan-Ling. Clinical and ATP7A gene analysis of three infants with Menkes disease and prenatal diagnosis for a fetus at risk[J]. Chinese Journal of Contemporary Pediatrics. 2014, 16(6): 624-628 https://doi.org/10.7499/j.issn.1008-8830.2014.06.013