Aminoacylase I deficiency due to ACY1 mRNA exon skipping

Authors

  • L. Ferri,

    1. Department of Neurosciences, Pharmacology and Child Health, University of Florence, Firenze, Italy
    2. Paediatric Neurology Unit and Laboratories, Neuroscience Department, Meyer Children's Hospital, Firenze, Italy
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    • These authors contributed equally.
  • S. Funghini,

    Corresponding author
    1. Paediatric Neurology Unit and Laboratories, Neuroscience Department, Meyer Children's Hospital, Firenze, Italy
    • Corresponding author: Silvia Funghini, Paediatric Neurology Unit and Laboratories, Meyer Children's Hospital, viale Pieraccini 24, 50139 Firenze, Italy.

      Tel.: +39 055 5662543;

      fax: +39 055 5662849;

      e-mail: s.funghini@meyer.it

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    • These authors contributed equally.
  • A. Fioravanti,

    1. Interdisciplinary Research Institute, USR 3078 CNRS, Universite' Lille Nord de France, Parc CNRS de la Haute Borne, Villeneuve d'Ascq, France
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  • E.G. Biondi,

    1. Interdisciplinary Research Institute, USR 3078 CNRS, Universite' Lille Nord de France, Parc CNRS de la Haute Borne, Villeneuve d'Ascq, France
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  • G. la Marca,

    1. Department of Neurosciences, Pharmacology and Child Health, University of Florence, Firenze, Italy
    2. Paediatric Neurology Unit and Laboratories, Neuroscience Department, Meyer Children's Hospital, Firenze, Italy
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  • R. Guerrini,

    1. Department of Neurosciences, Pharmacology and Child Health, University of Florence, Firenze, Italy
    2. Paediatric Neurology Unit and Laboratories, Neuroscience Department, Meyer Children's Hospital, Firenze, Italy
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  • M.A. Donati,

    1. Metabolic and Muscular Unit, Neuroscience Department, Meyer Children's Hospital, Firenze, Italy
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  • A. Morrone

    1. Department of Neurosciences, Pharmacology and Child Health, University of Florence, Firenze, Italy
    2. Paediatric Neurology Unit and Laboratories, Neuroscience Department, Meyer Children's Hospital, Firenze, Italy
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  • Nothing to declare.

Abstract

Aminoacylase 1 (ACY1) deficiency is a rare inborn error of metabolism of which less than 20 observations have been described. Patients exhibit urinary excretion of specific N-acetyl amino acids and manifest a heterogeneous clinical spectrum including intellectual disability, motor delay, seizures, moderate to severe mental retardation, absent speech, growth delay, muscular hypotonia and autistic features. Here, we report the case of ACY1 enzyme deficiency in a 6-year-old girl presenting severe intellectual disability, motor retardation, absence of spontaneous locomotor activity and severe speech delay. Urinary excretion of N-acetylated amino acids was present. Mutational analysis of ACY1 gene identified the new homozygous c.1001_1001+5del6 mutation, which alters the mRNA transcription leading to exon 13 skipping and inclusion of a premature stop codon (p.Lys308Glufs*7). A quantitative fluorescent multiplex-polymerase chain reaction (QFM-PCR) assay has been set up and confirmed homozygosity of the mutation in the patient's DNA. Biochemical analysis showed absence of ACY1 enzyme activity in the patient's fibroblasts. The structure of the mutated protein has been defined by homology modeling (HM). Our data endorse the hypothesis of a link between this inborn error of metabolism and the neurological manifestations observed in patients with ACY1 deficiency.

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