title: Identification of novel ATP7A mutations and prenatal diagnosis in Chinese patients with Menkes disease.
abstract: Menkes disease (MD) is a fatal X-linked multisystem disease caused by mutations in ATP7A. In this study, clinical and genetic analysis was performed in 24 male MD patients. Development delay, seizures, kinky coarse hair, and dystonia were found in 24, 22, 24, and 24 patients, respectively. Serum ceruloplasmin/copper tested in 19 patients was low. Abnormal classic features of MD presented in the MRI/MRA of 19 patients. Seventeen mutations of ATP7A were identified in 22 patients. Twelve were novel mutations including three small deletion/insertion, one missense mutation, two nonsense mutations, three splicing-site mutations, and three gross deletions. Twenty-two patients were genetically diagnosed; neither point mutation nor deletion/duplication was found in two of them. c.2179G > A found in five patients might be a hot-spot mutation. Prenatal molecular diagnosis was performed for five unrelated fetuses (1 female and 4 male), which found four fetuses to be wild type and one male carried the same mutation as the proband. This study of the largest sample of Chinese MD patients examined to date discovered the unique phenotype and genotype spectrum in Chinese patients with 12 novel mutations of ATP7A, and that c.2179G > A might be a hot-spot mutation in MD patients. Five successful prenatal diagnosis contributed important information for MD families.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, No. 1 Xi'anmen Street, West District, Beijing, 100034, China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Cao
authors.affiliation: Department of Pediatrics, Peking University First Hospital, No. 1 Xi'anmen Street, West District, Beijing, 100034, China.|Department of Neurology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, 030001, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Pediatrics, Peking University First Hospital, No. 1 Xi'anmen Street, West District, Beijing, 100034, China.|Department of Neurology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, 030001, China.
authors.forename: Yinyin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Peking University First Hospital, No. 1 Xi'anmen Street, West District, Beijing, 100034, China.|Department of Pediatrics, Peking University People's Hospital, Beijing, 100044, China.
authors.forename: Qionghui
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Pediatrics, Peking University First Hospital, No. 1 Xi'anmen Street, West District, Beijing, 100034, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Pediatrics, Peking University First Hospital, No. 1 Xi'anmen Street, West District, Beijing, 100034, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Gu
authors.affiliation: Department of Radiology, Peking University First Hospital, Beijing, 100034, China.
authors.forename: Jiangxi
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Obstetrics, Peking University First Hospital, Beijing, 100034, China.
authors.forename: Huixia
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Central Lab, Peking University First Hospital, Beijing, 100034, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Pan
authors.affiliation: Department of Obstetrics, Peking University First Hospital, Beijing, 100034, China.
authors.forename: Junya
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Obstetrics, Peking University First Hospital, Beijing, 100034, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Pediatrics, Peking University First Hospital, No. 1 Xi'anmen Street, West District, Beijing, 100034, China.|Department of Neurology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, 030001, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ren
authors.affiliation: Department of Pediatrics, Peking University First Hospital, No. 1 Xi'anmen Street, West District, Beijing, 100034, China.|Department of Epilepsy, Central Hospital of Jiamusi, Jiamusi University, Jiamusi, Heilongjiang Province, 154007, China.
authors.forename: Chengfeng
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Pediatrics, Peking University First Hospital, No. 1 Xi'anmen Street, West District, Beijing, 100034, China.|Department of Neurology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, 030001, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Pediatrics, Peking University First Hospital, No. 1 Xi'anmen Street, West District, Beijing, 100034, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pediatrics, Peking University First Hospital, No. 1 Xi'anmen Street, West District, Beijing, 100034, China.
authors.forename: Xingzhi
authors.initials: X
authors.lastname: Chang
authors.affiliation: Department of Pediatrics, Peking University First Hospital, No. 1 Xi'anmen Street, West District, Beijing, 100034, China.
authors.forename: Zhixian
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Pediatrics, Peking University First Hospital, No. 1 Xi'anmen Street, West District, Beijing, 100034, China.
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, 030001, China.
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Niu
authors.affiliation: Department of Epilepsy, Central Hospital of Jiamusi, Jiamusi University, Jiamusi, Heilongjiang Province, 154007, China.
authors.forename: Juli
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Peking University First Hospital, No. 1 Xi'anmen Street, West District, Beijing, 100034, China.
authors.forename: Xiru
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Pediatrics, Peking University First Hospital, No. 1 Xi'anmen Street, West District, Beijing, 100034, China. wang66jm@163.com.
authors.forename: Jingmin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Peking University First Hospital, No. 1 Xi'anmen Street, West District, Beijing, 100034, China. jiangyw@263.net.
authors.forename: Yuwu
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D002681:China; D000073840:Copper-Transporting ATPases / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008297:Male; D007706:Menkes Kinky Hair Syndrome / Q000175:diagnosis* / Q000235:genetics; D009154:Mutation; D011247:Pregnancy; D011296:Prenatal Diagnosis
chemical_list: D000073840:Copper-Transporting ATPases
keywords: ATP7A; Menkes disease; Mutations; Prenatal diagnosis