Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Attention-deficit/hyperactivity disorder (ADHD) is a common and highly heritable disorder, but specific genetic factors underlying risk remain elusive. To assess the role of structural variation in ADHD, we identified 222 inherited copy number variations (CNVs) within 335 ADHD patients and their parents that were not detected in 2026 unrelated healthy individuals. Although no excess CNVs, either deletions or duplications, were found in the ADHD cohort relative to controls, the inherited rare CNV-associated gene set was significantly enriched for genes reported as candidates in studies of autism, schizophrenia and Tourette syndrome, including A2BP1, AUTS2, CNTNAP2 and IMMP2L. The ADHD CNV gene set was also significantly enriched for genes known to be important for psychological and neurological functions, including learning, behavior, synaptic transmission and central nervous system development. Four independent deletions were located within the protein tyrosine phosphatase gene, PTPRD, recently implicated as a candidate gene for restless legs syndrome, which frequently presents with ADHD. A deletion within the glutamate receptor gene, GRM5, was found in an affected parent and all three affected offspring whose ADHD phenotypes closely resembled those of the GRM5 null mouse. Together, these results suggest that rare inherited structural variations play an important role in ADHD development and indicate a set of putative candidate genes for further study in the etiology of ADHD.
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PMID:Rare structural variants found in attention-deficit hyperactivity disorder are preferentially associated with neurodevelopmental genes. 1954 59

The Congress of the International Pediatric Sleep Association joint meeting with Pediatric Sleep Medicine Conference was held in Rome on December 3-5, 2010. It was chaired by the president of IPSA, prof. O. Bruni. About 400 participants taking part in 20 sessions could listen to lectures delivered by the most prominent specialists in pediatric sleep medicine. The presented issues related to sleep development, sleep-disordered breathing, abnormal behaviors and movements during sleep (restless legs syndrome, periodic limb movement disorder, bruxism), epilepsy, narcolepsy, insomnia, infant apnea, arousals and SIDS, sleep problems in children with other diseases (cancer, autism, ADHD, obesity), pharmacological treatment of pediatric sleep disorders, sleep habits, sleep education programs for children and families. This paper reports on the latest findings in the field of sleep medicine presented at the Congress. Particular attention was paid to practical issues in daily clinical work.
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PMID:[The current state of knowledge of pediatric sleep medicine. Report from the Congress of the International Pediatric Sleep Association (IPSA) joint meeting with Pediatric Sleep Medicine Conference (Rome, 2010)]. 2154 92

Research evidence increasingly points to the large impact of sleep disturbances on public health. Many aspects of sleep are heritable and genes influencing traits such as timing, EEG characteristics, sleep duration, and response to sleep loss have been identified. Notably, large-scale genome-wide analyses have implicated numerous genes with small effects on sleep timing. Additionally, there has been considerable progress in the identification of genes influencing risk for some neurological sleep disorders. For restless legs syndrome, implicated variants are typically in genes associated with neuronal development. By contrast, genes conferring risk for narcolepsy function in the immune system. Many genetic variants associated with sleep disorders are also implicated in neurological disorders in which sleep abnormalities are common; for example, variation in genes involved in synaptic homoeostasis are implicated in autism spectrum disorder and sleep-wake control. Further investigation into pleiotropic roles of genes influencing both sleep and neurological disorders could lead to new treatment strategies for a variety of sleep disturbances.
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PMID:Pleiotropic genetic effects influencing sleep and neurological disorders. 2810 51

Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability and the leading form of the monogenic cause of autism. Fragile X mental retardation type 1 (FMR1) gene premutation is the first single-gene cause of primary ovarian failure (Fragile X-associated primary ovarian insufficiency [FXPOI]) and one of the most common causes of ataxia (fragile X-associated tremor/ataxia syndrome [FXTAS]), multiple additional phenotypes such as fibromyalgia, hypothyroidism, migraine headaches, sleep disturbances, sleep apnea, restless legs syndrome, central pain syndrome, neuropathy and neuropsychiatric alterations has been described. Clinical involvement in men and women carrying the FMR1 premutation currently constitutes a real health problem in the society that should be taken into account. It is important to highlight that while in FXS there is a loss-of-function of the FMR1 gene, in premutation associated disorders there is a gain of FMR1 mRNA function. To date, the tremendous progress achieved in the understanding of the pathophysiology of FXS, has led to the development of several targeted therapies aimed at preventing or improving the neurological manifestations of the disease. This review is an update of the diseases associated with the FMR1 gene.
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PMID:Fragile X syndrome: An overview and update of the FMR1 gene. 2861 38

Neurodevelopmental disorders, including attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), are commonly associated with sleep disturbances. The etiology of sleep disorders is multifactorial, such as congenital vulnerability of the quality and quantity of sleep, congenital abnormality of the sleep-wake pattern, comorbid sleep problems with developmental disorders, and sleep disturbances associated with pharmacological treat- ment. Obstructive sleep apnea disorder (OSAS) and restless legs syndrome (RLS) are closely associated with ADHD. OSAS in children not only presents with symptoms of sleep distur- bances, but also with associated symptoms such as growth failure, neurocognitive and behav- ioral symptoms, ADHD-like symptoms, and enuresis. The first-line treatment is adenotonsillec- tomy. ADHD and RLS show high rates of comorbidity with common etiologies like iron defi- ciency and the alternation of dopamine transporter expression. Hypnotics are not effective for RLS, and a precise diagnosis is vital to treat RLS associated with ADHD. ASD is also associated with a high frequency of sleep disorders, especially insomnia, para- somnia, and sleep-wake disorders. The first strategy against sleep disturbances is behavioral intervention ; however, pharmacological treatment is sometimes needed. In clinical practice, excessive daytime sleepiness was reported in children with ADHD or ASD, which might lead to a deficit in alertness. Alertness deficits associated with neurodevel- opmental disorders remain uncertain, and so they should be assessed. The effect of stimulants on sleep in patients with ADHD differed among individuals, which might be the cause of insomnia and also treatment for ADHD and sleep hygiene. Non-stimu- lants are often effective for insomnia. Neurodevelopmental and sleep disorders are complex and bidirectional. Sleep disturbances should be taken into consideration in daily clinical practice.
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PMID:[The Diagnosis and Treatment of Sleep and Neurodevelopmental Disorders]. 3062 May

Sleep disturbances such as excessive daytime sleepiness, central and obstructive sleep apneas, restless legs syndrome, and rapid eye movement sleep dysregulation are prominent in patients with myotonic dystrophy type 1 (DM1). Mild intellectual deficits presented in many patients with DM1. In addition, psychosocial issues caused by neuropsychiatric symptoms are a clinical problem. We herein present the cases of four DM1 patients with sleep disturbances and neuropsychiatric symptoms in the preceding stage of clinically significant muscle symptoms. One of the cases exhibited a sleep disorder and neuropsychiatric symptoms before electromyography showed myotonic discharge, suggesting that careful follow-up is also important. Patients 1 and 2 were first referred to our department due to daytime sleepiness. Patients 3 and 4 were objectively suffering from daytime sleepiness of which they were not subjectively aware of. Patients 1, 3, and 4 obtained high apnea-hypopnea index (AHI) scores, which reflected central and/or obstructive apnea, whereas patient 2 had an AHI score of zero. The daytime cerebrospinal fluid (CSF) orexin levels of all patients ranged from the normal lower limit to low, although they were not as low as those observed in narcolepsy with typical cataplexy. Neuropsychological tests of patients 1 and 2 showed frontal lobe dysfunction. Patients 3 and 4 were diagnosed with mild intellectual disability and autism spectrum disorder, respectively. All patients exhibited indifference toward their own symptoms, which may have resulted from the cognitive decline caused by DM1. Based on family history and/or neurological findings such as myotonia, we suspected DM1 as the cause of their sleep disturbances. Molecular analysis using the triplet repeat-primed polymerase chain reaction (TP PCR) method and Southern blotting, which provided a genetic confirmation of the diagnosis of DM1, were performed. These clinical features of sleep disturbances were unrelated to the length of CTG repeats and are caused by unknown molecular mechanisms. Clinicians should take into account that multisystem involvement in DM1 is hugely variable, and thus, a disabling sleep disorder could overshadow muscle impairment in DM1 patients.
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PMID:Sleep Disorders in Four Patients With Myotonic Dystrophy Type 1. 3211