1. Genetic basis of hyperlysinemia.
- Author
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Houten, Sander M., Brinke, Heleen te, Denis, Simone, Ruiter, Jos P. N., Knegt, Alida C., de Klerk, Johannis B. C., Augoustides-Savvopoulou, Persephone, Häberle, Johannes, Baumgartner, Matthias R., Coskun, Turgay, Zschocke, Johannes, Sass, Jörn Oliver, Poll-The, Bwee Tien, Wanders, Ronald J. A., and Duran, Marinus
- Subjects
METABOLIC disorders ,GENETIC disorders ,LYSINE ,MISSENSE mutation ,GENETIC mutation - Abstract
Background: Hyperlysinemia is an autosomal recessive inborn error of L-lysine degradation. To date only one causal mutation in the gene encoding a-aminoadipic semialdehyde synthase has been reported. We aimed to AASS better define the genetic basis of hyperlysinemia. Methods: We collected the clinical, biochemical and molecular data in a cohort of 8 hyperlysinemia patients with distinct neurological features. Results: We found novel causal mutations in in all affected individuals, including 4 missense mutations, AASS 2 deletions and 1 duplication. In two patients originating from one family, the hyperlysinemia was caused by a contiguous gene deletion syndrome affecting and AASS and PTPRZ1 Conclusions: Hyperlysinemia is caused by mutations in AASS and PTPRZ1 hyperlysinemia is generally considered a benign AASS metabolic variant, the more severe neurological disease course in two patients with a contiguous deletion syndrome may be explained by the additional loss of PIPRZ1. Our findings illustrate the importance of detailed PTPRZ1 biochemical and genetic studies in any hyperlysinemia patient. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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