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Celestino-Soper, Patrícia B. S.; Violante, Sara; Crawford, Emily L.; Luo, Rui; Lionel, Anath C.; Delaby, Elsa; Cai, Guiqing; Sadikovic, Bekim; Lee, Kwanghyuk; Lo, Charlene; Gao, Kun; Person, Richard E.; Moss, Timothy J.; German, Jennifer R.; Huang, Ni; Shinawi, Marwan; Treadwell-Deering, Diane; Szatmari, Peter; Roberts, Wendy; Fernandez, Bridget; Schroer, Richard J.; Stevenson, Roger E.; Buxbaum, Joseph D.; Betancur, Catalina; [...]

A common X-linked inborn error of carnitine biosynthesis may be a risk factor for nondysmorphic autism

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  • Medientyp: E-Artikel
  • Titel: A common X-linked inborn error of carnitine biosynthesis may be a risk factor for nondysmorphic autism
  • Beteiligte: Celestino-Soper, Patrícia B. S.; Violante, Sara; Crawford, Emily L.; Luo, Rui; Lionel, Anath C.; Delaby, Elsa; Cai, Guiqing; Sadikovic, Bekim; Lee, Kwanghyuk; Lo, Charlene; Gao, Kun; Person, Richard E.; Moss, Timothy J.; German, Jennifer R.; Huang, Ni; Shinawi, Marwan; Treadwell-Deering, Diane; Szatmari, Peter; Roberts, Wendy; Fernandez, Bridget; Schroer, Richard J.; Stevenson, Roger E.; Buxbaum, Joseph D.; Betancur, Catalina; [...]
  • Erschienen: Proceedings of the National Academy of Sciences, 2012
  • Erschienen in: Proceedings of the National Academy of Sciences
  • Sprache: Englisch
  • DOI: 10.1073/pnas.1120210109
  • ISSN: 0027-8424; 1091-6490
  • Schlagwörter: Multidisciplinary
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:p> We recently reported a deletion of exon 2 of the trimethyllysine hydroxylase epsilon ( <jats:italic>TMLHE</jats:italic> ) gene in a proband with autism. <jats:italic>TMLHE</jats:italic> maps to the X chromosome and encodes the first enzyme in carnitine biosynthesis, 6- <jats:italic>N</jats:italic> -trimethyllysine dioxygenase. Deletion of exon 2 of <jats:italic>TMLHE</jats:italic> causes enzyme deficiency, resulting in increased substrate concentration (6- <jats:italic>N</jats:italic> -trimethyllysine) and decreased product levels (3-hydroxy-6- <jats:italic>N</jats:italic> -trimethyllysine and γ-butyrobetaine) in plasma and urine. <jats:italic>TMLHE</jats:italic> deficiency is common in control males (24 in 8,787 or 1 in 366) and was not significantly increased in frequency in probands from simplex autism families (9 in 2,904 or 1 in 323). However, it was 2.82-fold more frequent in probands from male-male multiplex autism families compared with controls (7 in 909 or 1 in 130; <jats:italic>P</jats:italic> = 0.023). Additionally, six of seven autistic male siblings of probands in male-male multiplex families had the deletion, suggesting that <jats:italic>TMLHE</jats:italic> deficiency is a risk factor for autism (metaanalysis Z-score = 2.90 and <jats:italic>P</jats:italic> = 0.0037), although with low penetrance (2–4%). These data suggest that dysregulation of carnitine metabolism may be important in nondysmorphic autism; that abnormalities of carnitine intake, loss, transport, or synthesis may be important in a larger fraction of nondysmorphic autism cases; and that the carnitine pathway may provide a novel target for therapy or prevention of autism. </jats:p>
  • Zugangsstatus: Freier Zugang