Corpus callosum agenesis, severe mental retardation, epilepsy, and dyskinetic quadriparesis due to a novel mutation in the homeodomain of ARX

Valerio Conti, Carla Marini, Simone Gana, Jyotsna Sudi, William B. Dobyns, Renzo Guerrini

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

We report on a patient with agenesis of the corpus callosum (ACC), severe mental retardation, infantile spasms and subsequent intractable epilepsy, spastic/dyskinetic quadriparesis, severe limb contractures, and scoliosis. This complex, newly described phenotype, is due to a novel non-conservative missense mutation in the ARX homeodomain (c.1072A>T; p.R358W), inherited from the unaffected mother. Differently from previously reported non-conservative mutations falling within the same domain, p.R358W did not cause XLAG. It is therefore possible that differences in clinical manifestations between our patient and those with XLAG, are related to the different position of the amino acid substitution in the homeodomain, or to the different chemical properties introduced by the substitution itself. To test the hypothesis that the patient's mother was asymptomatic because of non-random X chromosome inactivation (XCI), we performed DNA methylation studies of the human androgen receptor gene, demonstrating skewing of the XCI ratio (85:15). The complex phenotype described here combines different traits that had previously been linked to various ARX mutations, including conservative missense mutations in the homeodomain and expansion in the first ARX polyalanine tract and contributes to the expanding pleiotropy associated with ARX mutations.

Original languageEnglish
Pages (from-to)892-897
Number of pages6
JournalAmerican Journal of Medical Genetics, Part A
Volume155
Issue number4
DOIs
Publication statusPublished - Apr 2011

Fingerprint

Agenesis of Corpus Callosum
Quadriplegia
Intellectual Disability
X Chromosome Inactivation
Epilepsy
Missense Mutation
Mutation
Mothers
Phenotype
Infantile Spasms
Muscle Spasticity
Scoliosis
Contracture
DNA Methylation
Amino Acid Substitution
Extremities
Genes

Keywords

  • ARX novel mutation
  • Corpus callosum agenesis
  • Infantile spasms
  • Severe mental retardation
  • Spastic/dyskinetic quadriparesis

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Corpus callosum agenesis, severe mental retardation, epilepsy, and dyskinetic quadriparesis due to a novel mutation in the homeodomain of ARX. / Conti, Valerio; Marini, Carla; Gana, Simone; Sudi, Jyotsna; Dobyns, William B.; Guerrini, Renzo.

In: American Journal of Medical Genetics, Part A, Vol. 155, No. 4, 04.2011, p. 892-897.

Research output: Contribution to journalArticle

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