Biomedical subjects

Anne Philippe

Publications and source records attributed to Anne Philippe.

6 recordsLinked to original sources

PubMed2006

Involvement of hyperprolinemia in cognitive and psychiatric features of the 22q11 deletion syndrome.

Microdeletions of the 22q11 region, responsible for the velo-cardio-facial syndrome (VCFS), are associated with an increased risk for psychosis and mental retardation. Recently, it has been shown in a hyperprolinemic mouse model that an interaction between two genes localized in the hemideleted region, proline dehydrogenase (PRODH) and catechol-o-methyl-transferase (COMT), could be involved in this phenotype. Here, we further characterize in eight children the molecular basis of type I hyperprolinemia (HPI), a recessive disorder resulting from reduced activity of proline dehydrogenase (POX). We show that these patients present with mental retardation, epilepsy and, in some cases, psychiatric features. We next report that, among 92 adult or adolescent VCFS subjects, a subset of patients with severe hyperprolinemia has a phenotype distinguishable from that of other VCFS patients and reminiscent of HPI. Forward stepwise multiple regression analysis selected hyperprolinemia, psychosis and COMT genotype as independent variables influencing IQ in the whole VCFS sample. An inverse correlation between plasma proline level and IQ was found. In addition, as predicted from the mouse model, hyperprolinemic VCFS subjects bearing the Met-COMT low activity allele are at risk for psychosis (OR = 2.8, 95% CI = 1.04-7.4). Finally, from the extensive analysis of the PRODH gene coding sequence variations, it is predicted that POX residual activity in the 0-30% range results into HPI, whereas residual activity in the 30-50% range is associated either with normal plasma proline levels or with mild-to-moderate hyperprolinemia.

Adolescent↗

PubMed2005

Autism severity and temporal lobe functional abnormalities.

Two independent studies have described bilateral temporal hypoperfusion in autistic children. Temporal regions are implicated in social perception, language, and "theory-of-mind," abilities that are impaired in autism. We investigated a putative relationship between cerebral blood flow (rCBF) measured at rest and clinical profile of 45 autistic children (Autism Diagnostic Interview-Revised [ADI-R] scores). A whole-brain covariance analysis was performed. Significant negative correlation was observed between rCBF and ADI-R score in the left superior temporal gyrus. The more severe the autistic syndrome, the more rCBF is low in this region, suggesting that left superior temporal hypoperfusion is related to autistic behavior severity.

Autistic Disorder↗

PubMed2005

Effect of genetically caused excess of brain gamma-hydroxybutyric acid and GABA on sleep.

BACKGROUND: Exogenous gamma-hydroxybutyrate (GHB) increases slow-wave sleep and reduces daytime sleepiness and cataplexy in patients with primary narcolepsy. OBJECTIVE: To examine nighttime sleep and daytime sleepiness in a 13-year-old girl homozygous for succinic semialdehyde dehydrogenase (SSADH) deficiency, a rare recessive metabolic disorder that disrupts the normal degradation of 4-aminobutyric acid (GABA), and leads to an accumulation of GHB and GABA within the brain. METHODS: Sleep interview, nighttime polysomnography, Multiple Sleep Latency Tests, and continuous 24-hour in-lab recordings in the patient; overnight polysomnography in her recessive mother and in a 13-year-old female control. RESULTS: During quiet wakefulness, background electroencephalographic activity was slow and composed of 7-Hz activity. Sleep stage 3/4 was slightly increased (28.1% of total sleep period, norms 15%-28%), and the daytime mean sleep latency was short in the patient (3 minutes 42 seconds, norms > 8 minutes). Stage 2 spindles were infrequent in the child (0.18/minute, norms: 1.2-9.2/minute) and her mother (0.65/minute) but normal (4.6/minute) in the control. At the beginning of the second night, a tonic-clonic seizure occurred, followed by a dramatic increase in stage 3/4 sleep, that lasted 46.3 % of the total sleep period, double the normal value. The mother showed a reduced total sleep time and rapid eye movement sleep percentage. DISCUSSION: This suggests that a chronic excess of GABA and GHB induces subtle sleep abnormalities, whereas increased slow-wave sleep evoked by a sudden event (here an epileptic seizure) may be caused by a supplementary increase in GABA and GHB.

Adolescent↗

PubMed2004

Perception of complex sounds in autism: abnormal auditory cortical processing in children.

OBJECTIVE: The authors have previously described less activation of left speech-related temporal areas in adults with autism when listening to speech-like sounds than in normal adults. Here, they investigated whether this abnormal cortical processing was also present in children with primary autism. METHOD: Regional cerebral blood flow was measured with positron emission tomography after premedication in 11 autistic children and six nonautistic mentally retarded children during rest and while they were listening to speech-like sounds. RESULTS: As with autistic adults, direct comparison between the two groups revealed significantly less activation in the autistic group localized in left speech-related areas. CONCLUSIONS: For the first time to their knowledge, an activation study was performed in children with autism and has confirmed previous results obtained in adults. The abnormal cortical auditory processing observed in both children and adults with autism could be involved in inadequate behavioral responses to sounds and in language impairments characteristic of autism.

Acoustic Stimulation↗

PubMed2002

Investigation of two variants in the DOPA decarboxylase gene in patients with autism.

Though genetic risk factors are important for the development of autism, no specific risk alleles have yet been identified. DOPA decarboxylase (DDC) is involved in both the catecholaminergic and serotonergic pathways and may be considered a functional candidate gene for autism. The present study is the first to test if two new variants of possible functional significance in the DDC gene increase the susceptibility to autism. A total of 90 parent-offspring trios recruited in Denmark and France were investigated using the transmission disequilibrium test (TDT). We found no evidence of linkage disequilibrium between autism and either of the two polymorphisms. Nor did we find linkage disequilibrium between autism and haplotypes of the two variants using a multiallelic TDT. These findings suggest that the DDC gene is unlikely to play a major role in the development of autism in our data set.

Adolescent↗

PubMed2002

Analysis of ten candidate genes in autism by association and linkage.

We studied the possible involvement of ten candidate genes in autism: proenkephalin, prodynorphin, and proprotein convertase subtilisin/kexin type 2 (opioid metabolism); tyrosine hydroxylase, dopamine receptors D2 and D5, monoamine oxidases A and B (monoaminergic system); brain-derived neurotrophic factor, and neural cell adhesion molecule (involved in neurodevelopment). Thirty-eight families with two affected siblings and one family with two affected half-siblings, recruited by the Paris Autism Research International Sibpair Study (PARIS), were tested using the transmission disequilibrium test and two-point affected sib-pair linkage analysis. We found no evidence for association or linkage with intragenic or linked markers. Our family sample has good power for detecting a linkage disequilibrium of 0.80. Thus, these genes are unlikely to play a major role in the families studied, but further studies in a much larger sample would be needed to highlight weaker genetic effects.

Alleles↗