title: Intragenic deletions of ALDH7A1 in pyridoxine-dependent epilepsy caused by Alu-Alu recombination.
abstract: OBJECTIVE
  To investigate the role of intragenic deletions of ALDH7A1 in patients with clinical and biochemical evidence of pyridoxine-dependent epilepsy but only a single identifiable mutation in ALDH7A1.
  
  
  METHODS
  We designed a custom oligonucleotide array with high-density probe coverage across the ALDH7A1 gene. We performed array comparative genomic hybridization in 6 patients with clinical and biochemical evidence of pyridoxine-dependent epilepsy but only a single detectable mutation in ALDH7A1 by sequence analysis.
  
  
  RESULTS
  We found partial deletions of ALDH7A1 in 5 of 6 patients. Breakpoint analysis reveals that the deletions are likely a result of Alu-Alu recombination in all cases. The density of Alu elements within introns of ALDH7A1 suggests susceptibility to recurrent rearrangement.
  
  
  CONCLUSIONS
  Patients with clinical pyridoxine-dependent epilepsy and a single identifiable mutation in ALDH7A1 warrant further investigation for copy number changes involving the ALHD7A1 gene.
authors.affiliation: From the Department of Pediatrics, Division of Genetic Medicine (H.C.M., M.Z., E.G., J.C.), and the Departments of Neurology and Pediatrics, Division of Pediatric Neurology (S.M.G.), University of Washington, Seattle; the Division of Genetic Medicine (H.C.M.), Seattle Children's Hospital, WA; the Centre for Translational Omics, Genetics, and Genomic Medicine (P.T.C., P.B.M.), UCL Institute of Child Health, London, UK; the Department of Pediatrics (K.P., B.P.), Division of Child Neurology, University Hospital Graz, Austria; the Division of Child Neurology (B.P.), University Children's Hospital Zurich, University of Zurich, Switzerland; the Departments of Pediatrics and Neurology (D.R.N.), Northwestern University Feinberg School of Medicine, Evanston, IL; the Departments of Pediatrics and Neurology (D.R.N.), Ann & Robert H. Lurie Children's Hospital of Chicago, IL; and the Departments of Neurology and Pediatrics, Division of Pediatric Neurology (S.M.G.), Seattle Children's Hospital, WA. sgospe@uw.edu hmefford@uw.edu.
authors.forename: Heather C
authors.initials: HC
authors.lastname: Mefford
authors.affiliation: From the Department of Pediatrics, Division of Genetic Medicine (H.C.M., M.Z., E.G., J.C.), and the Departments of Neurology and Pediatrics, Division of Pediatric Neurology (S.M.G.), University of Washington, Seattle; the Division of Genetic Medicine (H.C.M.), Seattle Children's Hospital, WA; the Centre for Translational Omics, Genetics, and Genomic Medicine (P.T.C., P.B.M.), UCL Institute of Child Health, London, UK; the Department of Pediatrics (K.P., B.P.), Division of Child Neurology, University Hospital Graz, Austria; the Division of Child Neurology (B.P.), University Children's Hospital Zurich, University of Zurich, Switzerland; the Departments of Pediatrics and Neurology (D.R.N.), Northwestern University Feinberg School of Medicine, Evanston, IL; the Departments of Pediatrics and Neurology (D.R.N.), Ann & Robert H. Lurie Children's Hospital of Chicago, IL; and the Departments of Neurology and Pediatrics, Division of Pediatric Neurology (S.M.G.), Seattle Children's Hospital, WA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Zemel
authors.affiliation: From the Department of Pediatrics, Division of Genetic Medicine (H.C.M., M.Z., E.G., J.C.), and the Departments of Neurology and Pediatrics, Division of Pediatric Neurology (S.M.G.), University of Washington, Seattle; the Division of Genetic Medicine (H.C.M.), Seattle Children's Hospital, WA; the Centre for Translational Omics, Genetics, and Genomic Medicine (P.T.C., P.B.M.), UCL Institute of Child Health, London, UK; the Department of Pediatrics (K.P., B.P.), Division of Child Neurology, University Hospital Graz, Austria; the Division of Child Neurology (B.P.), University Children's Hospital Zurich, University of Zurich, Switzerland; the Departments of Pediatrics and Neurology (D.R.N.), Northwestern University Feinberg School of Medicine, Evanston, IL; the Departments of Pediatrics and Neurology (D.R.N.), Ann & Robert H. Lurie Children's Hospital of Chicago, IL; and the Departments of Neurology and Pediatrics, Division of Pediatric Neurology (S.M.G.), Seattle Children's Hospital, WA.
authors.forename: Eileen
authors.initials: E
authors.lastname: Geraghty
authors.affiliation: From the Department of Pediatrics, Division of Genetic Medicine (H.C.M., M.Z., E.G., J.C.), and the Departments of Neurology and Pediatrics, Division of Pediatric Neurology (S.M.G.), University of Washington, Seattle; the Division of Genetic Medicine (H.C.M.), Seattle Children's Hospital, WA; the Centre for Translational Omics, Genetics, and Genomic Medicine (P.T.C., P.B.M.), UCL Institute of Child Health, London, UK; the Department of Pediatrics (K.P., B.P.), Division of Child Neurology, University Hospital Graz, Austria; the Division of Child Neurology (B.P.), University Children's Hospital Zurich, University of Zurich, Switzerland; the Departments of Pediatrics and Neurology (D.R.N.), Northwestern University Feinberg School of Medicine, Evanston, IL; the Departments of Pediatrics and Neurology (D.R.N.), Ann & Robert H. Lurie Children's Hospital of Chicago, IL; and the Departments of Neurology and Pediatrics, Division of Pediatric Neurology (S.M.G.), Seattle Children's Hospital, WA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Cook
authors.affiliation: From the Department of Pediatrics, Division of Genetic Medicine (H.C.M., M.Z., E.G., J.C.), and the Departments of Neurology and Pediatrics, Division of Pediatric Neurology (S.M.G.), University of Washington, Seattle; the Division of Genetic Medicine (H.C.M.), Seattle Children's Hospital, WA; the Centre for Translational Omics, Genetics, and Genomic Medicine (P.T.C., P.B.M.), UCL Institute of Child Health, London, UK; the Department of Pediatrics (K.P., B.P.), Division of Child Neurology, University Hospital Graz, Austria; the Division of Child Neurology (B.P.), University Children's Hospital Zurich, University of Zurich, Switzerland; the Departments of Pediatrics and Neurology (D.R.N.), Northwestern University Feinberg School of Medicine, Evanston, IL; the Departments of Pediatrics and Neurology (D.R.N.), Ann & Robert H. Lurie Children's Hospital of Chicago, IL; and the Departments of Neurology and Pediatrics, Division of Pediatric Neurology (S.M.G.), Seattle Children's Hospital, WA.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Clayton
authors.affiliation: From the Department of Pediatrics, Division of Genetic Medicine (H.C.M., M.Z., E.G., J.C.), and the Departments of Neurology and Pediatrics, Division of Pediatric Neurology (S.M.G.), University of Washington, Seattle; the Division of Genetic Medicine (H.C.M.), Seattle Children's Hospital, WA; the Centre for Translational Omics, Genetics, and Genomic Medicine (P.T.C., P.B.M.), UCL Institute of Child Health, London, UK; the Department of Pediatrics (K.P., B.P.), Division of Child Neurology, University Hospital Graz, Austria; the Division of Child Neurology (B.P.), University Children's Hospital Zurich, University of Zurich, Switzerland; the Departments of Pediatrics and Neurology (D.R.N.), Northwestern University Feinberg School of Medicine, Evanston, IL; the Departments of Pediatrics and Neurology (D.R.N.), Ann & Robert H. Lurie Children's Hospital of Chicago, IL; and the Departments of Neurology and Pediatrics, Division of Pediatric Neurology (S.M.G.), Seattle Children's Hospital, WA.
authors.forename: Karl
authors.initials: K
authors.lastname: Paul
authors.affiliation: From the Department of Pediatrics, Division of Genetic Medicine (H.C.M., M.Z., E.G., J.C.), and the Departments of Neurology and Pediatrics, Division of Pediatric Neurology (S.M.G.), University of Washington, Seattle; the Division of Genetic Medicine (H.C.M.), Seattle Children's Hospital, WA; the Centre for Translational Omics, Genetics, and Genomic Medicine (P.T.C., P.B.M.), UCL Institute of Child Health, London, UK; the Department of Pediatrics (K.P., B.P.), Division of Child Neurology, University Hospital Graz, Austria; the Division of Child Neurology (B.P.), University Children's Hospital Zurich, University of Zurich, Switzerland; the Departments of Pediatrics and Neurology (D.R.N.), Northwestern University Feinberg School of Medicine, Evanston, IL; the Departments of Pediatrics and Neurology (D.R.N.), Ann & Robert H. Lurie Children's Hospital of Chicago, IL; and the Departments of Neurology and Pediatrics, Division of Pediatric Neurology (S.M.G.), Seattle Children's Hospital, WA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Plecko
authors.affiliation: From the Department of Pediatrics, Division of Genetic Medicine (H.C.M., M.Z., E.G., J.C.), and the Departments of Neurology and Pediatrics, Division of Pediatric Neurology (S.M.G.), University of Washington, Seattle; the Division of Genetic Medicine (H.C.M.), Seattle Children's Hospital, WA; the Centre for Translational Omics, Genetics, and Genomic Medicine (P.T.C., P.B.M.), UCL Institute of Child Health, London, UK; the Department of Pediatrics (K.P., B.P.), Division of Child Neurology, University Hospital Graz, Austria; the Division of Child Neurology (B.P.), University Children's Hospital Zurich, University of Zurich, Switzerland; the Departments of Pediatrics and Neurology (D.R.N.), Northwestern University Feinberg School of Medicine, Evanston, IL; the Departments of Pediatrics and Neurology (D.R.N.), Ann & Robert H. Lurie Children's Hospital of Chicago, IL; and the Departments of Neurology and Pediatrics, Division of Pediatric Neurology (S.M.G.), Seattle Children's Hospital, WA.
authors.forename: Philippa B
authors.initials: PB
authors.lastname: Mills
authors.affiliation: From the Department of Pediatrics, Division of Genetic Medicine (H.C.M., M.Z., E.G., J.C.), and the Departments of Neurology and Pediatrics, Division of Pediatric Neurology (S.M.G.), University of Washington, Seattle; the Division of Genetic Medicine (H.C.M.), Seattle Children's Hospital, WA; the Centre for Translational Omics, Genetics, and Genomic Medicine (P.T.C., P.B.M.), UCL Institute of Child Health, London, UK; the Department of Pediatrics (K.P., B.P.), Division of Child Neurology, University Hospital Graz, Austria; the Division of Child Neurology (B.P.), University Children's Hospital Zurich, University of Zurich, Switzerland; the Departments of Pediatrics and Neurology (D.R.N.), Northwestern University Feinberg School of Medicine, Evanston, IL; the Departments of Pediatrics and Neurology (D.R.N.), Ann & Robert H. Lurie Children's Hospital of Chicago, IL; and the Departments of Neurology and Pediatrics, Division of Pediatric Neurology (S.M.G.), Seattle Children's Hospital, WA.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Nordli
authors.affiliation: From the Department of Pediatrics, Division of Genetic Medicine (H.C.M., M.Z., E.G., J.C.), and the Departments of Neurology and Pediatrics, Division of Pediatric Neurology (S.M.G.), University of Washington, Seattle; the Division of Genetic Medicine (H.C.M.), Seattle Children's Hospital, WA; the Centre for Translational Omics, Genetics, and Genomic Medicine (P.T.C., P.B.M.), UCL Institute of Child Health, London, UK; the Department of Pediatrics (K.P., B.P.), Division of Child Neurology, University Hospital Graz, Austria; the Division of Child Neurology (B.P.), University Children's Hospital Zurich, University of Zurich, Switzerland; the Departments of Pediatrics and Neurology (D.R.N.), Northwestern University Feinberg School of Medicine, Evanston, IL; the Departments of Pediatrics and Neurology (D.R.N.), Ann & Robert H. Lurie Children's Hospital of Chicago, IL; and the Departments of Neurology and Pediatrics, Division of Pediatric Neurology (S.M.G.), Seattle Children's Hospital, WA. sgospe@uw.edu hmefford@uw.edu.
authors.forename: Sidney M
authors.initials: SM
authors.lastname: Gospe
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D004827:Epilepsy / Q000235:genetics*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D017384:Sequence Deletion
chemical_list: C089507:ALDH7A1 protein, human; D000444:Aldehyde Dehydrogenase