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Genetic variations of the melatonin pathway in patients with attention-deficit and hyperactivity disorders.

Chaste, Pauline; Clement, Nathalie; Botros, Hany Goubran; Guillaume, Jean-Luc; Konyukh, Marina; Pagan, Cécile; Scheid, Isabelle; Nygren, Gudrun; Anckarsäter, Henrik LU and Råstam, Maria LU , et al. (2011) In Journal of Pineal Research 51(4). p.394-399
Abstract
Melatonin is a powerful antioxidant and a synchronizer of many physiological processes. Alteration in melatonin signaling has been reported in a broad range of diseases, but little is known about the genetic variability of this pathway in humans. Here, we sequenced all the genes of the melatonin pathway -AA-NAT, ASMT, MTNR1A, MTNR1B and GPR50 - in 321 individuals from Sweden including 101 patients with attention-deficit/hyperactivity disorder (ADHD) and 220 controls from the general population. We could find several damaging mutations in patients with ADHD, but no significant enrichment compared with the general population. Among these variations, we found a splice site mutation in ASMT (IVS5+2T>C) and one stop mutation in MTNR1A... (More)
Melatonin is a powerful antioxidant and a synchronizer of many physiological processes. Alteration in melatonin signaling has been reported in a broad range of diseases, but little is known about the genetic variability of this pathway in humans. Here, we sequenced all the genes of the melatonin pathway -AA-NAT, ASMT, MTNR1A, MTNR1B and GPR50 - in 321 individuals from Sweden including 101 patients with attention-deficit/hyperactivity disorder (ADHD) and 220 controls from the general population. We could find several damaging mutations in patients with ADHD, but no significant enrichment compared with the general population. Among these variations, we found a splice site mutation in ASMT (IVS5+2T>C) and one stop mutation in MTNR1A (Y170X) - detected exclusively in patients with ADHD - for which biochemical analyses indicated that they abolish the activity of ASMT and MTNR1A. These genetic and functional results represent the first comprehensive ascertainment of melatonin signaling deficiency in ADHD. (Less)
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Melatonin is a powerful antioxidant and a synchronizer of many physiological processes. Alteration of melatonin signaling has been reported in a broad range of diseases, but little is known about the genetic variability of this pathway in humans. Here, we sequenced all the genes of the melatonin pathway - AA-NAT, ASMT, MTNR1A, MTNR1B and GPR50 - in 321 individuals from Sweden including 101 patients with Attention Deficit/Hyperactivity Disorder (ADHD) and 220 controls from the general population. We could find several damaging mutations in patients with ADHD, but no significant enrichment compared with the general population. Among these variations, we found a splice site mutation in ASMT (IVS5+2T>C) and one stop mutation in MTNR1A (Y170X) — detected exclusively in patients with ADHD — for which biochemical analyses indicated that they abolish the activity of ASMT and MTNR1A. These genetic and functional results represent the first comprehensive ascertainment of melatonin signaling deficiency in ADHD.
in
Journal of Pineal Research
volume
51
issue
4
pages
394 - 399
publisher
Wiley-Blackwell
external identifiers
  • wos:000298013500004
  • pmid:21615493
  • scopus:80054800543
ISSN
1600-079X
DOI
10.1111/j.1600-079X.2011.00902.x
language
English
LU publication?
yes
id
356cdf87-8fa2-4485-b341-b77ba37120f8 (old id 1972109)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21615493?dopt=Abstract
http://onlinelibrary.wiley.com/doi/10.1111/j.1600-079X.2011.00902.x/abstract?systemMessage=W
date added to LUP
2011-06-07 22:46:52
date last changed
2017-09-17 08:07:35
@article{356cdf87-8fa2-4485-b341-b77ba37120f8,
  abstract     = {Melatonin is a powerful antioxidant and a synchronizer of many physiological processes. Alteration in melatonin signaling has been reported in a broad range of diseases, but little is known about the genetic variability of this pathway in humans. Here, we sequenced all the genes of the melatonin pathway -AA-NAT, ASMT, MTNR1A, MTNR1B and GPR50 - in 321 individuals from Sweden including 101 patients with attention-deficit/hyperactivity disorder (ADHD) and 220 controls from the general population. We could find several damaging mutations in patients with ADHD, but no significant enrichment compared with the general population. Among these variations, we found a splice site mutation in ASMT (IVS5+2T>C) and one stop mutation in MTNR1A (Y170X) - detected exclusively in patients with ADHD - for which biochemical analyses indicated that they abolish the activity of ASMT and MTNR1A. These genetic and functional results represent the first comprehensive ascertainment of melatonin signaling deficiency in ADHD.},
  author       = {Chaste, Pauline and Clement, Nathalie and Botros, Hany Goubran and Guillaume, Jean-Luc and Konyukh, Marina and Pagan, Cécile and Scheid, Isabelle and Nygren, Gudrun and Anckarsäter, Henrik and Råstam, Maria and Ståhlberg, Ola and Gillberg, I Carina and Melke, Jonas and Delorme, Richard and Leblond, Claire and Toro, Roberto and Huguet, Guillaume and Fauchereau, Fabien and Durand, Christelle and Boudarene, Lydia and Serrano, Emilie and Lemière, Nathalie and Launay, Jean Marie and Leboyer, Marion and Jockers, Ralf and Gillberg, Christopher and Bourgeron, Thomas},
  issn         = {1600-079X},
  keyword      = {Melatonin is a powerful antioxidant and a synchronizer of many physiological processes. Alteration of melatonin signaling has been reported in a broad range of diseases,but little is known about the genetic variability of this pathway in humans. Here,we sequenced all the genes of the melatonin pathway - AA-NAT,ASMT,MTNR1A,MTNR1B and GPR50 - in 321 individuals from Sweden including 101 patients with Attention Deficit/Hyperactivity Disorder (ADHD) and 220 controls from the general population. We could find several damaging mutations in patients with ADHD,but no significant enrichment compared with the general population. Among these variations,we found a splice site mutation in ASMT (IVS5+2T>C) and one stop mutation in MTNR1A (Y170X) — detected exclusively in patients with ADHD — for which biochemical analyses indicated that they abolish the activity of ASMT and MTNR1A. These genetic and functional results represent the first comprehensive ascertainment of melatonin signaling deficiency in ADHD.},
  language     = {eng},
  number       = {4},
  pages        = {394--399},
  publisher    = {Wiley-Blackwell},
  series       = {Journal of Pineal Research},
  title        = {Genetic variations of the melatonin pathway in patients with attention-deficit and hyperactivity disorders.},
  url          = {http://dx.doi.org/10.1111/j.1600-079X.2011.00902.x},
  volume       = {51},
  year         = {2011},
}