How to cite this article: Siggberg L, Mustonen A, Schuit R, Salomons GS, Roos B, Gibson KM, Jakobs C, Ignatius J, Knuutila S. 2011. Familial 6p22.2 Duplication Associates With Mild Developmental Delay and Increased SSADH Activity. Am J Med Genet Part B 156:448–453.
Familial 6p22.2 duplication associates with mild developmental delay and increased SSADH activity†
Article first published online: 22 MAR 2011
Copyright © 2011 Wiley-Liss, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 156, Issue 4, pages 448–453, June 2011
How to Cite
Siggberg, L., Mustonen, A., Schuit, R., Salomons, G. S., Roos, B., Gibson, K. M., Jakobs, C., Ignatius, J. and Knuutila, S. (2011), Familial 6p22.2 duplication associates with mild developmental delay and increased SSADH activity. Am. J. Med. Genet., 156: 448–453. doi: 10.1002/ajmg.b.31180
- Issue published online: 25 APR 2011
- Article first published online: 22 MAR 2011
- Manuscript Accepted: 18 FEB 2011
- Manuscript Received: 22 SEP 2010
- Rinnekoti Research Foundation
- Medicinska Understödsföreningen Liv och hälsa rf
- Nylands Nation
- State Appropriations of Helsinki and Uusimaa Hospital District
- NIH. Grant Numbers: NS40270, HD58553
- duplication 6p22.2;
- mild mental retardation
We present a family with mild developmental delay and a duplication (6)(p22.2). Array CGH analyses revealed this 0.7 Mb duplication in all three patients, spanning candidate genes ALDH5A1, DCDC2, and KIAA0319. Results were confirmed by MLPA analysis of the dyslexia genes DCDC2 and KIAA0319. Of interest, ALDH5A1 encodes succinate semialdehyde dehydrogenase (SSADH), an enzyme responsible for γ-amino-butyric acid (GABA) degradation. Inherited deficiency of SSADH results in accumulation of the neuromodulator γ-hydroxybutyrate (GHB), which likely contributes to some aspects of the neurological phenotype of SSADH deficiency (MIM #271980). Based on autosomal-recessive inheritance, we sequenced ALDH5A1 in all patients, which revealed no pathogenic mutations. SSADH enzyme studies in cultured white cells confirmed elevated SSADH activity, consistent with the duplication, whereas concentrations of SSA were slightly elevated in urine, suggesting oxidant stress. We speculate that the duplication (6)(p22.2) and corresponding hyperactive level of SSADH activity may have negative consequences for GABA metabolism and the role of SSADH in other metabolic sequences. © 2011 Wiley-Liss, Inc.