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 language | English |
|---|---|
| Pages (from-to) | 144-148 |
| Number of pages | 5 |
| Journal | Gene |
| Volume | 559 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Apr 1 2015 |
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Keywords
- DDC
- Intellectual disability
- Whole exome sequencing
ASJC Scopus subject areas
- Genetics
- Medicine(all)
Cite this
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 journal › Article
}
TY - JOUR
T1 - Syndromic intellectual disability
T2 - A new phenotype caused by an aromatic amino acid decarboxylase gene (DDC) variant
AU - Graziano, Claudio
AU - Wischmeijer, Anita
AU - Pippucci, Tommaso
AU - Fusco, Carlo
AU - Diquigiovanni, Chiara
AU - Nõukas, Margit
AU - Sauk, Martin
AU - Kurg, Ants
AU - Rivieri, Francesca
AU - Blau, Nenad
AU - Hoffmann, Georg F.
AU - Chaubey, Alka
AU - Schwartz, Charles E.
AU - Romeo, Giovanni
AU - Bonora, Elena
AU - Garavelli, Livia
AU - Seri, Marco
PY - 2015/4/1
Y1 - 2015/4/1
N2 - 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.
AB - 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.
KW - DDC
KW - Intellectual disability
KW - Whole exome sequencing
UR - http://www.scopus.com/inward/record.url?scp=84922431765&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84922431765&partnerID=8YFLogxK
U2 - 10.1016/j.gene.2015.01.026
DO - 10.1016/j.gene.2015.01.026
M3 - Article
C2 - 25597765
AN - SCOPUS:84922431765
VL - 559
SP - 144
EP - 148
JO - Gene
JF - Gene
SN - 0378-1119
IS - 2
ER -