title: Genetic basis of hyperlysinemia.
abstract: BACKGROUND
  Hyperlysinemia is an autosomal recessive inborn error of L-lysine degradation. To date only one causal mutation in the AASS gene encoding α-aminoadipic semialdehyde synthase has been reported. We aimed to 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 AASS in all affected individuals, including 4 missense mutations, 2 deletions and 1 duplication. In two patients originating from one family, the hyperlysinemia was caused by a contiguous gene deletion syndrome affecting AASS and PTPRZ1.
  
  
  CONCLUSIONS
  Hyperlysinemia is caused by mutations in AASS. As hyperlysinemia is generally considered a benign metabolic variant, the more severe neurological disease course in two patients with a contiguous deletion syndrome may be explained by the additional loss of PTPRZ1. Our findings illustrate the importance of detailed biochemical and genetic studies in any hyperlysinemia patient.
authors.affiliation: Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam, AZ 1105, The Netherlands. s.m.houten@amc.uva.nl
authors.forename: Sander M
authors.initials: SM
authors.lastname: Houten
authors.forename: Heleen
authors.initials: H
authors.lastname: Te Brinke
authors.forename: Simone
authors.initials: S
authors.lastname: Denis
authors.forename: Jos Pn
authors.initials: JP
authors.lastname: Ruiter
authors.forename: Alida C
authors.initials: AC
authors.lastname: Knegt
authors.forename: Johannis Bc
authors.initials: JB
authors.lastname: de Klerk
authors.forename: Persephone
authors.initials: P
authors.lastname: Augoustides-Savvopoulou
authors.forename: Johannes
authors.initials: J
authors.lastname: Häberle
authors.forename: Matthias R
authors.initials: MR
authors.lastname: Baumgartner
authors.forename: Turgay
authors.initials: T
authors.lastname: Coşkun
authors.forename: Johannes
authors.initials: J
authors.lastname: Zschocke
authors.forename: Jörn Oliver
authors.initials: JO
authors.lastname: Sass
authors.forename: Bwee Tien
authors.initials: BT
authors.lastname: Poll-The
authors.forename: Ronald Ja
authors.initials: RJ
authors.lastname: Wanders
authors.forename: Marinus
authors.initials: M
authors.lastname: Duran
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D015331:Cohort Studies; D055028:Comparative Genomic Hybridization; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D020167:Hyperlysinemias / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D012443:Saccharopine Dehydrogenases / Q000235:genetics
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; C043044:AASS protein, human; D012443:Saccharopine Dehydrogenases