TPH2 G/T polymorphism is associated with hyperphagia, IQ, and internalizing problems in Prader–Willi syndrome / Elisabeth M. DYKENS in Journal of Child Psychology and Psychiatry, 52-5 (May 2011)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 52-5 (May 2011) . - p.580-587 Titre : TPH2 G/T polymorphism is associated with hyperphagia, IQ, and internalizing problems in Prader–Willi syndrome Type de document : texte imprimé Auteurs : Elisabeth M. DYKENS, Auteur ; Elizabeth ROOF, Auteur ; Douglas BITTEL, Auteur ; Merlin G. BUTLER, Auteur Année de publication : 2011 Article en page(s) : p.580-587 Langues : Anglais (eng) Mots-clés : Behavior problems  genetics  intelligence  internalizing disorder  neurochemistry  Prader–Willi syndrome Index. décimale : PER Périodiques Résumé : Background:  Prader–Willi syndrome (PWS) is a genetic, neurodevelopmental disorder characterized by intellectual disabilities, growth hormone dysregulation, hyperphagia, increased risks of morbid obesity, compulsive behaviors, and irritability. As aberrant serotonergic functioning is strongly implicated in PWS, we examined associations between the PWS phenotype and polymorphisms in tryptophan hydroxylase 2 (TPH2), the rate-limiting enzyme in the biosynthesis of serotonin in the brain. Methods:  Ninety-two individuals with PWS aged 4 to 50 years (M = 21.97) were genotyped for the TPH2 G703-T polymorphism. IQ testing was conducted in offspring, and parents completed questionnaires that tapped their child’s compulsivity, hyperphagia, and other behavior problems. Results:  As expected, the frequency of G/T or T/T polymorphisms in participants with PWS (39%) was similar to rates found in the general population (38%). Compared to those with a homozygous (G/G) genotype, individuals with a T allele had significantly higher hyperphagic behavior, drive, and severity scores, and they also had a younger age of onset of hyperphagia. Those with a T allele also had higher IQ scores than their counterparts. Females with a T allele had significantly higher internalizing symptoms, primarily anxiety and depression, than all others. Conclusions:  TPH2 G/T polymorphisms, and presumed loss of enzyme function, were associated with specific aspects of the PWS phenotype. Aberrant serotonergic functioning is strongly implicated in hyperphagia in PWS, and females with TPH2 T alleles may be at higher risk for affective or mood disorders. Findings hold promise for examining other serotonin-altering genes in PWS, and for future serotonin-altering treatment trials. En ligne : http://dx.doi.org/10.1111/j.1469-7610.2011.02365.x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=121 [article] TPH2 G/T polymorphism is associated with hyperphagia, IQ, and internalizing problems in Prader–Willi syndrome [texte imprimé] / Elisabeth M. DYKENS, Auteur ; Elizabeth ROOF, Auteur ; Douglas BITTEL, Auteur ; Merlin G. BUTLER, Auteur . - 2011 . - p.580-587. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 52-5 (May 2011) . - p.580-587 Mots-clés : Behavior problems  genetics  intelligence  internalizing disorder  neurochemistry  Prader–Willi syndrome Index. décimale : PER Périodiques Résumé : Background:  Prader–Willi syndrome (PWS) is a genetic, neurodevelopmental disorder characterized by intellectual disabilities, growth hormone dysregulation, hyperphagia, increased risks of morbid obesity, compulsive behaviors, and irritability. As aberrant serotonergic functioning is strongly implicated in PWS, we examined associations between the PWS phenotype and polymorphisms in tryptophan hydroxylase 2 (TPH2), the rate-limiting enzyme in the biosynthesis of serotonin in the brain. Methods:  Ninety-two individuals with PWS aged 4 to 50 years (M = 21.97) were genotyped for the TPH2 G703-T polymorphism. IQ testing was conducted in offspring, and parents completed questionnaires that tapped their child’s compulsivity, hyperphagia, and other behavior problems. Results:  As expected, the frequency of G/T or T/T polymorphisms in participants with PWS (39%) was similar to rates found in the general population (38%). Compared to those with a homozygous (G/G) genotype, individuals with a T allele had significantly higher hyperphagic behavior, drive, and severity scores, and they also had a younger age of onset of hyperphagia. Those with a T allele also had higher IQ scores than their counterparts. Females with a T allele had significantly higher internalizing symptoms, primarily anxiety and depression, than all others. Conclusions:  TPH2 G/T polymorphisms, and presumed loss of enzyme function, were associated with specific aspects of the PWS phenotype. Aberrant serotonergic functioning is strongly implicated in hyperphagia in PWS, and females with TPH2 T alleles may be at higher risk for affective or mood disorders. Findings hold promise for examining other serotonin-altering genes in PWS, and for future serotonin-altering treatment trials. En ligne : http://dx.doi.org/10.1111/j.1469-7610.2011.02365.x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=121

TPH2 polymorphisms and expression in Prader-Willi syndrome subjects with differing genetic subtypes / Rebecca S. HENKHAUS in Journal of Neurodevelopmental Disorders, 2-3 (September 2010)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 2-3 (September 2010) . - p.144-8 Titre : TPH2 polymorphisms and expression in Prader-Willi syndrome subjects with differing genetic subtypes Type de document : texte imprimé Auteurs : Rebecca S. HENKHAUS, Auteur ; Douglas C. BITTEL, Auteur ; Merlin G. BUTLER, Auteur Article en page(s) : p.144-8 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Prader-Willi syndrome (PWS) is a genetic imprinting disease that causes developmental and behavioral disturbances resulting from loss of expression of genes from the paternal chromosome 15q11-q13 region. In about 70% of subjects, this portion of the paternal chromosome is deleted, while 25% have two copies of the maternal chromosome 15, or uniparental maternal disomy (UPD; the remaining subjects have imprinting center defects. There are several documented physical and behavioral differences between the two major PWS genetic subtypes (deletion and UPD) indicating the genetic subtype plays a role in clinical presentation. Serotonin is known to be disturbed in PWS and affects both eating behavior and compulsion, which are reported to be abnormal in PWS. We investigated the tryptophan hydroxylase gene (TPH2), the rate-limiting enzyme in the production of brain serotonin, by analyzing three different TPH2 gene polymorphisms, transcript expression, and correlation with PWS genetic subtype. DNA and RNA from lymphoblastoid cell lines derived from 12 PWS and 12 comparison subjects were used for the determination of genetic subtype, TPH2 polymorphisms and quantitative RT-PCR analysis. A similar frequency of TPH2 polymorphisms was seen in the PWS and comparison subjects with PWS deletion subjects showing increased expression with one or more TPH2 polymorphism. Both PWS deletion and PWS UPD subjects had significantly lower TPH2 expression than control subjects and PWS deletion subjects had significantly lower TPH2 expression compared with PWS UPD subjects. PWS subjects with 15q11-q13 deletions had lower TPH2 expression compared with PWS UPD or control subjects, requiring replication and further studies to identify the cause including identification of disturbed gene interactions resulting from the deletion process. En ligne : http://dx.doi.org/10.1007/s11689-010-9051-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=342 [article] TPH2 polymorphisms and expression in Prader-Willi syndrome subjects with differing genetic subtypes [texte imprimé] / Rebecca S. HENKHAUS, Auteur ; Douglas C. BITTEL, Auteur ; Merlin G. BUTLER, Auteur . - p.144-8. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 2-3 (September 2010) . - p.144-8 Index. décimale : PER Périodiques Résumé : Prader-Willi syndrome (PWS) is a genetic imprinting disease that causes developmental and behavioral disturbances resulting from loss of expression of genes from the paternal chromosome 15q11-q13 region. In about 70% of subjects, this portion of the paternal chromosome is deleted, while 25% have two copies of the maternal chromosome 15, or uniparental maternal disomy (UPD; the remaining subjects have imprinting center defects. There are several documented physical and behavioral differences between the two major PWS genetic subtypes (deletion and UPD) indicating the genetic subtype plays a role in clinical presentation. Serotonin is known to be disturbed in PWS and affects both eating behavior and compulsion, which are reported to be abnormal in PWS. We investigated the tryptophan hydroxylase gene (TPH2), the rate-limiting enzyme in the production of brain serotonin, by analyzing three different TPH2 gene polymorphisms, transcript expression, and correlation with PWS genetic subtype. DNA and RNA from lymphoblastoid cell lines derived from 12 PWS and 12 comparison subjects were used for the determination of genetic subtype, TPH2 polymorphisms and quantitative RT-PCR analysis. A similar frequency of TPH2 polymorphisms was seen in the PWS and comparison subjects with PWS deletion subjects showing increased expression with one or more TPH2 polymorphism. Both PWS deletion and PWS UPD subjects had significantly lower TPH2 expression than control subjects and PWS deletion subjects had significantly lower TPH2 expression compared with PWS UPD subjects. PWS subjects with 15q11-q13 deletions had lower TPH2 expression compared with PWS UPD or control subjects, requiring replication and further studies to identify the cause including identification of disturbed gene interactions resulting from the deletion process. En ligne : http://dx.doi.org/10.1007/s11689-010-9051-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=342

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