Syndromic intellectual disability: A new phenotype caused by an aromatic amino acid decarboxylase gene (DDC) variant

Claudio Graziano, Anita Wischmeijer, Tommaso Pippucci, Carlo Fusco, Chiara Diquigiovanni, Margit Nõukas, Martin Sauk, Ants Kurg, Francesca Rivieri, Nenad Blau, Georg F. Hoffmann, Alka Chaubey, Charles E. Schwartz, Giovanni Romeo, Elena Bonora, Livia Garavelli, Marco Seri

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The causative variant in a consanguineous family in which the three patients (two siblings and a cousin) presented with intellectual disability, Marfanoid habitus, craniofacial dysmorphisms, chronic diarrhea and progressive kyphoscoliosis, has been identified through whole exome sequencing (WES) analysis. WES study identified a homozygous DDC variant in the patients, c.1123C>T, resulting in p.Arg375Cys missense substitution.Mutations in DDC cause a recessive metabolic disorder (aromatic amino acid decarboxylase, AADC, deficiency, OMIM #608643) characterized by hypotonia, oculogyric crises, excessive sweating, temperature instability, dystonia, severe neurologic dysfunction in infancy, and specific abnormalities of neurotransmitters and their metabolites in the cerebrospinal fluid (CSF). In our family, analysis of neurotransmitters and their metabolites in patient's CSF shows a pattern compatible with AADC deficiency, although the clinical signs are different from the classic form. Our work expands the phenotypic spectrum associated with DDC variants, which therefore can cause an additional novel syndrome without typical movement abnormalities.

Original languageEnglish
Pages (from-to)144-148
Number of pages5
JournalGene
Volume559
Issue number2
DOIs
Publication statusPublished - Apr 1 2015

Fingerprint

Aromatic-L-Amino-Acid Decarboxylases
Intellectual Disability
Exome
Phenotype
Neurotransmitter Agents
Cerebrospinal Fluid
Genes
Genetic Databases
Muscle Hypotonia
Sweating
Dystonia
Neurologic Manifestations
Siblings
Diarrhea
Mutation
Temperature

Keywords

  • DDC
  • Intellectual disability
  • Whole exome sequencing

ASJC Scopus subject areas

  • Genetics
  • Medicine(all)

Cite this

Graziano, C., Wischmeijer, A., Pippucci, T., Fusco, C., Diquigiovanni, C., Nõukas, M., ... Seri, M. (2015). Syndromic intellectual disability: A new phenotype caused by an aromatic amino acid decarboxylase gene (DDC) variant. Gene, 559(2), 144-148. https://doi.org/10.1016/j.gene.2015.01.026

Syndromic intellectual disability : A new phenotype caused by an aromatic amino acid decarboxylase gene (DDC) variant. / Graziano, Claudio; Wischmeijer, Anita; Pippucci, Tommaso; Fusco, Carlo; Diquigiovanni, Chiara; Nõukas, Margit; Sauk, Martin; Kurg, Ants; Rivieri, Francesca; Blau, Nenad; Hoffmann, Georg F.; Chaubey, Alka; Schwartz, Charles E.; Romeo, Giovanni; Bonora, Elena; Garavelli, Livia; Seri, Marco.

In: Gene, Vol. 559, No. 2, 01.04.2015, p. 144-148.

Research output: Contribution to journalArticle

Graziano, C, Wischmeijer, A, Pippucci, T, Fusco, C, Diquigiovanni, C, Nõukas, M, Sauk, M, Kurg, A, Rivieri, F, Blau, N, Hoffmann, GF, Chaubey, A, Schwartz, CE, Romeo, G, Bonora, E, Garavelli, L & Seri, M 2015, 'Syndromic intellectual disability: A new phenotype caused by an aromatic amino acid decarboxylase gene (DDC) variant', Gene, vol. 559, no. 2, pp. 144-148. https://doi.org/10.1016/j.gene.2015.01.026
Graziano C, Wischmeijer A, Pippucci T, Fusco C, Diquigiovanni C, Nõukas M et al. Syndromic intellectual disability: A new phenotype caused by an aromatic amino acid decarboxylase gene (DDC) variant. Gene. 2015 Apr 1;559(2):144-148. https://doi.org/10.1016/j.gene.2015.01.026
Graziano, Claudio ; Wischmeijer, Anita ; Pippucci, Tommaso ; Fusco, Carlo ; Diquigiovanni, Chiara ; Nõukas, Margit ; Sauk, Martin ; Kurg, Ants ; Rivieri, Francesca ; Blau, Nenad ; Hoffmann, Georg F. ; Chaubey, Alka ; Schwartz, Charles E. ; Romeo, Giovanni ; Bonora, Elena ; Garavelli, Livia ; Seri, Marco. / Syndromic intellectual disability : A new phenotype caused by an aromatic amino acid decarboxylase gene (DDC) variant. In: Gene. 2015 ; Vol. 559, No. 2. pp. 144-148.
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