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Screening of human LPHN3 for variants with a potential impact on ADHD susceptibility.

Abstract

Attention deficit hyperactivity disorder (ADHD) is the most common behavioral disorder in childhood, and often has effects detectable into adulthood. Advances in genetic linkage and association analysis have begun to elucidate some of the genetic factors underlying this complex disorder. Recently, we identified LPHN3, a novel ADHD susceptibility gene harbored in 4q, and showed that a LPHN3 common haplotype confers susceptibility to ADHD and predicts effectiveness of stimulant medication. Here we present the mutational analysis of the entire coding region of LPHN3 in a cohort of 139 ADHD subjects and 52 controls from across the USA. We identified 21 variants, of which 14 have been reported and 7 are novel. These include 5 missense, 8 synonymous, and 8 intronic changes. Interestingly, neither susceptibility nor protective haplotype alleles are associated with obviously significant coding region changes, or canonical splice site alterations, suggesting that non-coding variations determining the quantity and/or quality of LPHN3 isoforms are the likely contributors to this common behavioral disorder.

Authors+Show Affiliations

Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892-3717, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Intramural

Language

eng

PubMed ID

21184580

Citation

Domené, Sabina, et al. "Screening of Human LPHN3 for Variants With a Potential Impact On ADHD Susceptibility." American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics, vol. 156B, no. 1, 2011, pp. 11-8.
Domené S, Stanescu H, Wallis D, et al. Screening of human LPHN3 for variants with a potential impact on ADHD susceptibility. Am J Med Genet B Neuropsychiatr Genet. 2011;156B(1):11-8.
Domené, S., Stanescu, H., Wallis, D., Tinloy, B., Pineda, D. E., Kleta, R., ... Muenke, M. (2011). Screening of human LPHN3 for variants with a potential impact on ADHD susceptibility. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics, 156B(1), pp. 11-8. doi:10.1002/ajmg.b.31141.
Domené S, et al. Screening of Human LPHN3 for Variants With a Potential Impact On ADHD Susceptibility. Am J Med Genet B Neuropsychiatr Genet. 2011;156B(1):11-8. PubMed PMID: 21184580.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Screening of human LPHN3 for variants with a potential impact on ADHD susceptibility. AU - Domené,Sabina, AU - Stanescu,Horia, AU - Wallis,Deeann, AU - Tinloy,Bradford, AU - Pineda,Daniel E, AU - Kleta,Robert, AU - Arcos-Burgos,Mauricio, AU - Roessler,Erich, AU - Muenke,Maximilian, Y1 - 2010/11/12/ PY - 2010/08/04/received PY - 2010/10/18/accepted PY - 2010/12/25/entrez PY - 2010/12/25/pubmed PY - 2011/4/5/medline SP - 11 EP - 8 JF - American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics JO - Am. J. Med. Genet. B Neuropsychiatr. Genet. VL - 156B IS - 1 N2 - Attention deficit hyperactivity disorder (ADHD) is the most common behavioral disorder in childhood, and often has effects detectable into adulthood. Advances in genetic linkage and association analysis have begun to elucidate some of the genetic factors underlying this complex disorder. Recently, we identified LPHN3, a novel ADHD susceptibility gene harbored in 4q, and showed that a LPHN3 common haplotype confers susceptibility to ADHD and predicts effectiveness of stimulant medication. Here we present the mutational analysis of the entire coding region of LPHN3 in a cohort of 139 ADHD subjects and 52 controls from across the USA. We identified 21 variants, of which 14 have been reported and 7 are novel. These include 5 missense, 8 synonymous, and 8 intronic changes. Interestingly, neither susceptibility nor protective haplotype alleles are associated with obviously significant coding region changes, or canonical splice site alterations, suggesting that non-coding variations determining the quantity and/or quality of LPHN3 isoforms are the likely contributors to this common behavioral disorder. SN - 1552-485X UR - https://www.unboundmedicine.com/medline/citation/21184580/Screening_of_human_LPHN3_for_variants_with_a_potential_impact_on_ADHD_susceptibility_ L2 - https://doi.org/10.1002/ajmg.b.31141 DB - PRIME DP - Unbound Medicine ER -