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A novel DDC gene deletion mutation in two Chinese mainland siblings with aromatic l-amino acid decarboxylase deficiency

  • Lifang Dai
    Affiliations
    Department of Neurology, Beijing Children's Hospital, Capital Medical University, National Center For Children's Health, 100045, China
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Changhong Ding
    Correspondence
    Corresponding authors at: Department of Neurology, Beijing Children's Hospital, Capital Medical University, National Center For Children's Health China, 100045 Nanlishi Road No 56, Xi Strict, Beijing, China.
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Neurology, Beijing Children's Hospital, Capital Medical University, National Center For Children's Health, 100045, China
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this work.
    Fang Fang
    Correspondence
    Corresponding authors at: Department of Neurology, Beijing Children's Hospital, Capital Medical University, National Center For Children's Health China, 100045 Nanlishi Road No 56, Xi Strict, Beijing, China.
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Neurology, Beijing Children's Hospital, Capital Medical University, National Center For Children's Health, 100045, China
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this work.

      Abstract

      Background

      Aromatic l-amino acid decarboxylase (AADC) deficiency (OMIM #608643) is a rare and severe disorder of biogenic amine synthesis caused by mutations in the DDC gene. The phenomenology of the movement disorder includes intermittent oculogyric crises and limb dystonia, generalized athetosis, and impaired voluntary movement.

      Objective

      To identify clinical manifestations and DDC gene mutations in two Chinese mainland children who are siblings with AADC deficiency.

      Methods

      We used targeted next-generation sequencing and quantitative polymerase chain reaction (qPCR) to reveal DDC mutations in these children.

      Results

      Two DDC gene mutations were found: one missense mutation, c.1040G > A (p.Arg347Gln), is a reported mutation derived from the mother; the other mutation, a whole-exon 11 and 12 deletion, is a novel mutation derived from the father. The index patient and her brother both had poor sucking power and feeding difficulty at birth and episodes of oculogyric crises, truncal hypotonia, limb hypertonia, sleep disturbances, irritability, and motor delay. The siblings both died at 1 year and 10 months due to asphyxia and pneumonia during gaze and hypertonia episodes.

      Conclusion

      This study identified a novel DDC gene deletion mutation in two siblings with AADC deficiency disease in the Chinese mainland population.

      Keywords

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