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Metabolic Brain Disease

, Volume 32, Issue 4, pp 1123–1131 | Cite as

Identification of novel ATP7A mutations and prenatal diagnosis in Chinese patients with Menkes disease

  • Binbin Cao
  • Xiaoping Yang
  • Yinyin Chen
  • Qionghui Huang
  • Ye Wu
  • Qiang Gu
  • Jiangxi Xiao
  • Huixia Yang
  • Hong Pan
  • Junya Chen
  • Yu Sun
  • Li Ren
  • Chengfeng Zhao
  • Yanhua Deng
  • Yanling Yang
  • Xingzhi Chang
  • Zhixian Yang
  • Yuehua Zhang
  • Zhengping Niu
  • Juli Wang
  • Xiru Wu
  • Jingmin WangEmail author
  • Yuwu JiangEmail author
Original Article

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.

Keywords

Menkes disease ATP7A Mutations Prenatal diagnosis 

Notes

Acknowledgements

We thank all the patients and their families for their cooperation. We also thank Helene Lawler revising the manuscript. This research was supported by the grants from The National Key Research and Development Program of China (No. 2016YFC0901500 (2016YFC0901505), The National Key Research Project“12-5” (No:2012BAI09B04), Beijing key laboratory of molecular diagnosis and study on pediatric genetic diseases (No:Z141107004414036).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Binbin Cao
    • 1
  • Xiaoping Yang
    • 1
    • 2
  • Yinyin Chen
    • 1
    • 2
  • Qionghui Huang
    • 1
    • 3
  • Ye Wu
    • 1
  • Qiang Gu
    • 1
  • Jiangxi Xiao
    • 4
  • Huixia Yang
    • 5
  • Hong Pan
    • 6
  • Junya Chen
    • 5
  • Yu Sun
    • 5
  • Li Ren
    • 1
    • 2
  • Chengfeng Zhao
    • 1
    • 7
  • Yanhua Deng
    • 1
    • 2
  • Yanling Yang
    • 1
  • Xingzhi Chang
    • 1
  • Zhixian Yang
    • 1
  • Yuehua Zhang
    • 1
  • Zhengping Niu
    • 2
  • Juli Wang
    • 7
  • Xiru Wu
    • 1
  • Jingmin Wang
    • 1
    Email author
  • Yuwu Jiang
    • 1
    Email author
  1. 1.Department of PediatricsPeking University First HospitalBeijingChina
  2. 2.Department of NeurologyFirst Hospital of Shanxi Medical UniversityTaiyuanChina
  3. 3.Department of PediatricsPeking University People’s HospitalBeijingChina
  4. 4.Department of RadiologyPeking University First HospitalBeijingChina
  5. 5.Department of ObstetricsPeking University First HospitalBeijingChina
  6. 6.Department of Central LabPeking University First HospitalBeijingChina
  7. 7.Department of Epilepsy, Central Hospital of JiamusiJiamusi UniversityJiamusiChina

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