Intellectual Disability and Hemizygous GPD2 Mutation
Article first published online: 29 MAR 2013
Copyright © 2013 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 161, Issue 5, pages 1044–1050, May 2013
How to Cite
2013. Intellectual disability and hemizygous GPD2 mutation. Am J Med Genet Part A 161A:1044–1050., , , , , , .
- Issue published online: 22 APR 2013
- Article first published online: 29 MAR 2013
- Manuscript Accepted: 20 DEC 2012
- Manuscript Received: 18 JUL 2012
- array techniques;
- Next Generation Sequencing;
- intellectual disability;
We report on a 25-year-old female with intellectual disability, mildly unusual face, and a pervasive developmental disorder, in whom routine aCGH showed a 298 kb de novo deletion at chromosome 2q24.1(156869529–157167986 × 1). The region contained two genes (NR4A2; GPD2). Molecular studies in the proposita showed an additional variant in GPD2 (c.614C > T, p.Pro205Leu), which was predicted to be pathogenic. The variant was also present in the healthy mother and sister. Functional analysis showed absent GPD2 activity in the proposita and 50% activity in mother and sister. We conclude that we have been able to find circumstantial evidence for the causative effect of the hemizygous GPD2 mutation but full proof remained lacking. Total costs for the work-up in these patients were high (€21,975 [$27,029]). Similar results will increasingly be found when Next Generation Techniques will be applied widely in patients with intellectual disability, and proving pathogenicity by functional studies or in animal models will be expensive. We advocate the use of freely accessible international databases combining phenotype and genotype data using standard nomenclatures to facilitate proving pathogenicity of research data and to decrease costs of health care. © 2013 Wiley Periodicals, Inc.