The research was prospectively reviewed and approved by a duly constituted ethics committee (IRB 00007816 AOU Meyer IRB #2).
Article first published online: 17 MAR 2011
Copyright © 2011 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 155, Issue 4, pages 892–897, April 2011
How to Cite
Conti, V., Marini, C., Gana, S., Sudi, J., Dobyns, W. B. and Guerrini, R. (2011), Corpus callosum agenesis, severe mental retardation, epilepsy, and dyskinetic quadriparesis due to a novel mutation in the homeodomain of ARX. Am. J. Med. Genet., 155: 892–897. doi: 10.1002/ajmg.a.33923
How to Cite this Article: Conti V, Marini C, Gana S, Sudi J, Dobyns WB, Guerrini R. 2011. Corpus callosum agenesis, severe mental retardation, epilepsy, and dyskinetic quadriparesis due to a novel mutation in the homeodomain of ARX. Am J Med Genet Part A 155:892–897.
- Issue published online: 24 MAR 2011
- Article first published online: 17 MAR 2011
- Manuscript Accepted: 10 JAN 2011
- Manuscript Received: 11 NOV 2010
- Italian Ministry of Health. Grant Number: Research Project Ex Art. 56/05/13 L 289/2002
- Sixth Framework Programme of the EU. Grant Number: LSH-CT-2006-037315
- National Institutes of Health. Grant Number: 1R01-NS046616
- ARX novel mutation;
- spastic/dyskinetic quadriparesis;
- corpus callosum agenesis;
- severe mental retardation;
- infantile spasms
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. © 2011 Wiley-Liss, Inc.