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AMPD1 functional variants associated with autism in Han Chinese population

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Abstract

Autism is a childhood neurodevelopmental disorder with high heterogeneity. Following our genome-wide associated loci with autism, we performed sequencing analysis of the coding regions, UTR and flanking splice junctions of AMPD1 in 830 Chinese autism individuals as well as 514 unrelated normal controls. Fourteen novel variants in the coding sequence were identified, including 11 missense variants and 3 synonymous mutations. Among these missense variants, 10 variants were absent in 514 control subjects, and conservative and functional prediction was carried out. Mitochondria activity and lactate dehydrogenase assay were performed in 5 patients’ lymphoblast cell lines; p.P572S and p.S626C showed decreased mitochondrial complex I activity, and p.S626C increased lactate dehydrogenase release in medium. Conclusively, our data suggested that mutational variants in AMPD1 contribute to autism risk in Han Chinese population, uncovering the contribution of mutant protein to disease development that operates via mitochondria dysfunction and cell necrosis.

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Acknowledgments

We would like to thank our patients and their family for participating in the study, and thank Prof. Jia da Li and Fengyu Zhang for providing comments that improve manuscript. We also thank laboratory colleagues for the help and advices during the experiment. This work was supported by National Basic Research Program of China (2012CB517902), National Natural Science Foundation of China (81330027, 81161120544) and National Key Technology R&D Program of China (2012BAI03B02).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. State Key Laboratory of Medical Genetics, Central South University, 110, Xiangya Road, Changsha, Hunan, China

    Lusi Zhang, Xiaojuan Xu, Yu Peng, Hui Guo, Yongcheng Pan, Jingjing Chen, Tianyun Wang, Hao Peng, Qiong Liu, Di Tian, Qian Pan, Jingping Zhao, Zhengmao Hu & Kun Xia

  2. School of Life Sciences, Central South University, Changsha, Hunan, China

    Lusi Zhang, Yu Peng, Hui Guo & Kun Xia

  3. Mental Health Institute, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China

    Jianjun Ou & Jingping Zhao

  4. Key Laboratory of Medical Information Research, Central South University, Changsha, Hunan, China

    Kun Xia

  5. Department of Pediatrics, No. 3 Hospital of the Sun Yat-sen University, Guangzhou, Guangdong, China

    Xiaobin Zou

  6. The Reproductive Medicine Hospital of the First Hospital of Lanzhou University, Lanzhou, Gansu, China

    Xiaojuan Xu

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  1. Lusi Zhang
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Correspondence to Zhengmao Hu or Kun Xia.

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Zhang, L., Ou, J., Xu, X. et al. AMPD1 functional variants associated with autism in Han Chinese population. Eur Arch Psychiatry Clin Neurosci 265, 511–517 (2015). https://doi.org/10.1007/s00406-014-0524-6

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  • DOI: https://doi.org/10.1007/s00406-014-0524-6

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