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)

The serotonin receptor 2B gene (HTR2B; MIM 601122) is a pharmacological and positional candidate gene in early-onset obsessive-compulsive disorder. Sequences of a putative promoter region and splice regions were first elucidated, then sequenced along with HTR2B coding regions. Probands from seven families included in a previous genome scan in which one of the strongest linkage findings was to a region including HTR2B, along with two genomic DNA pools of 10 unrelated control subjects and 10 unrelated autism probands were screened. One single nucleotide polymorphism was found in intron 1, that may be useful as a marker in genetic linkage and association studies. It does not appear likely to affect splicing. No evidence for functional mutation was found in the sequenced regions of HTR2B.
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PMID:Mutation screening of human 5-HT(2B)receptor gene in early-onset obsessive-compulsive disorder. 1072 92

Because of the recent identification of several mutations of methyl-CpG-binding protein 2 (MECP2) in patients with Rett syndrome (RTT), a patient with suspected RTT from an autism clinic was screened for mutations. She was found to have a novel heterozygous nonsense mutation, 129C>T (Q19X), which leads to the most severely truncated MECP2 protein reported to date. Sequencing of parental DNA revealed the mutation was de novo. The patient was not affected with microcephaly or hyperventilation, but had other features of Rett syndrome including severe mental retardation and symptoms of autistic disorder. Moderately skewed X-chromosome inactivation (XCI) may have contributed to her relatively mild phenotype.
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PMID:Novel de novo nonsense mutation of MECP2 in a patient with Rett syndrome. 1073 89

NESP55, a novel member of the chromogranins, was originally implicated as a precursor of a peptide LSAL with 5-HT1B receptor antagonist activity. In humans, NESP55 (MIM 139320) is encoded by an alternative transcript of GNAS1, the gene encoding the guanine nucleotide-binding alpha subunit of G(S). As a result of the potential relevance of NESP55 to serotoninergic neurotransmission, we screened its sequence using genomic DNA pools from autistic disorder, obsessive-compulsive disorder (OCD) probands and control subjects. Six single nucleotide polymorphisms (SNPs) were identified and the allele frequencies of those SNPs were determined. In addition, a 24-bp in-frame deletion in the coding region was found in one of the OCD probands. To further investigate its pattern of inheritance and the relevance to studied phenotypes, we genotyped 123 total subjects from autism, OCD and attention deficit hyperactivity disorder (ADHD) families. The deletion was detected only in one OCD family and followed Mendelian inheritance. All subjects with the deletion were heterozygous. However, there are no specific behavioural or physical alterations in the subjects with this deletion variant. The physiological role of NESP55 in serotoninergic neurotransmission as well as the effect of the deletion on its function should be evaluated in future studies.
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PMID:Deletion polymorphism in the coding region of the human NESP55 alternative transcript of GNAS1. 1086 Jul 17

We report a family with a heterogeneous group of neurologic disorders associated with the mitochondrial DNA G8363A transfer ribonucleic acid (RNA)Lys mutation. The phenotype of one child in the family was consistent with autism. During his second year of life, he lost previously acquired language skills and developed marked hyperactivity with toe-walking, abnormal reciprocal social interaction, stereotyped mannerisms, restricted interests, self-injurious behavior, and seizures. Brain magnetic resonance imaging (MRI) and repeated serum lactate studies were normal. His older sister developed signs of Leigh syndrome with progressive ataxia, myoclonus, seizures, and cognitive regression. Her laboratory studies revealed increased MRI T2-weighted signal in the putamen and posterior medulla, elevated lactate in serum and cerebrospinal fluid, and absence of cytochrome c oxidase staining in muscle histochemistry. Molecular analysis in her revealed the G8363A mutation of the mitochondrial transfer RNA(Lys) gene in blood (82% mutant mitochondrial DNA) and muscle (86%). The proportions of mutant mitochondrial DNA from her brother with autism were lower (blood 60%, muscle 61%). It is likely that the origin of his autism phenotype is the pathogenic G8363A mitochondrial DNA mutation. This observation suggests that certain mitochondrial point mutations could be the basis for autism in some individuals.
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PMID:Autism associated with the mitochondrial DNA G8363A transfer RNA(Lys) mutation. 1086 77

The results of genetic linkage studies for autism have suggested that a susceptibility locus for the disease is located on the long arm of chromosome 7 (7q). An autistic individual carrying a translocation, t(7;13)(q31.3;q21), with the chromosome 7 breakpoint located in the region of 7q implicated by genetic studies was identified. A novel gene known as "RAY1" (or "FAM4A1") was found to be directly interrupted by the translocation breakpoint. The gene, which was found to be encoded by 16 exons with evidence of alternative splicing, spanned > or =220 kb of DNA at 7q31.3. Mutation screening of the entire coding region in a set of 27 unrelated autistic individuals failed to identify phenotype-specific variants, suggesting that coding region mutations are unlikely to be involved in the etiology of autism. Apparent homologues of RAY1 have also been identified in mouse, rat, pig, chicken, fruit fly, and nematode. The human and mouse genes share similar splicing patterns, and their predicted protein products are 98% identical.
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PMID:Identification of a novel gene on chromosome 7q31 that is interrupted by a translocation breakpoint in an autistic individual. 1088 44

We have identified a one megabase deletion in the 15q22-15q23 region in a patient with autism, developmental delay, and mild dysmorphism. Genes that map within the deletion region and genes that are interrupted or rearranged at the deletion breakpoints are candidate genes for autism. Fluroescence in situ hybridization studies in this patient revealed that part or all of the PML gene is absent from one chromosome 15 and a BAC clone containing the D15S124 gene locus hybridizes to only one chromosome 15. BAC clones containing the PTPN9, and SLP-1[hUNC24] genes showed markedly reduced hybridization in the 15q22-q23 region on one chromosome 15 in the patient. These BACs also hybridize to the 15q11-q13 region in close proximity to SNRPN and HERC2, and in this region there is equal intensity of signal on the normal and on the deleted chromosome. There are previous reports of deletions and duplications of the 15q11-q13 region in patients with autism. Our patient represents the first report of a 15q22-q23 deletion. Hybridization of the PTPN9 and Slp-1 Bac clones to the 15q11-q13 and the 15q22-q23 regions of chromosome 15 may be due to the presence of PTPN9 or SLP-1 gene sequences or to the presence of other gene sequences or to non-coding homologous DNA sequences. The PTPN9 gene encodes a non-receptor protein tyrosine phosphatase. The Slp-1 [hUNC24] gene is expressed mainly in the brain. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:765-770, 2000.
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PMID:Analysis of a 1-megabase deletion in 15q22-q23 in an autistic patient: identification of candidate genes for autism and of homologous DNA segments in 15q22-q23 and 15q11-q13. 1112 Nov 77

We have sequenced 1949 kb from the terminal Giemsa light band of human chromosome 16p, enabling us to fully annotate the region extending from the telomeric repeats to the previously published tuberous sclerosis disease 2 (TSC2) and polycystic kidney disease 1 (PKD1) genes. This region can be subdivided into two GC-rich, Alu-rich domains and one GC-rich, Alu-poor domain. The entire region is extremely gene rich, containing 100 confirmed genes and 20 predicted genes. Many of the genes encode widely expressed proteins orchestrating basic cellular processes (e.g. DNA recombination, repair, transcription, RNA processing, signal transduction, intracellular signalling and mRNA translation). Others, such as the alpha globin genes (HBA1 and HBA2), PDIP and BAIAP3, are specialized tissue-restricted genes. Some of the genes have been previously implicated in the pathophysiology of important human genetic diseases (e.g. asthma, cataracts and the ATR-16 syndrome). Others are known disease genes for alpha thalassaemia, adult polycystic kidney disease and tuberous sclerosis. There is also linkage evidence for bipolar affective disorder, epilepsy and autism in this region. Sixty-three chromosomal deletions reported here and elsewhere allow us to interpret the results of removing progressively larger numbers of genes from this well defined human telomeric region.
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PMID:Sequence, structure and pathology of the fully annotated terminal 2 Mb of the short arm of human chromosome 16. 1115 97

Gilles de la Tourette syndrome (GTS) is a complex neuropsychiatric disorder characterized by multiple motor and phonic tics. We identified a male patient with GTS and other anomalies. It was determined that he carried a de novo duplication of the long arm of chromosome 7 [46,XY,dup(7)(q22.1-q31.1)]. Further molecular analysis revealed that the duplication was inverted. The distal chromosomal breakpoint occurred between the two genetic markers D7S515 and D7S522, which define a region previously shown to be disrupted in a familiar case of GTS. Yeast and bacterial artificial chromosome clones spanning the breakpoints were identified by means of FISH analysis. To further characterize the distal breakpoint for a role in GTS, we performed Southern blot hybridization analysis and identified a 6.5-kb SacI junction fragment in the patient's genomic DNA. The DNA sequence of this fragment revealed two different breaks in 7q31 within a region of approximately 500 kb. IMMP2L, a novel gene coding for the apparent human homologue of the yeast mitochondrial inner membrane peptidase subunit 2, was found to be disrupted by both the breakpoint in the duplicated fragment and the insertion site in 7q31. The cDNA of the human IMMP2L gene was cloned, and analysis of the complete 1,522-bp transcript revealed that it encompassed six exons spanning 860 kb. The possible role of IMMP2L and several other candidate genes within the region of chromosomal rearrangement, including NRCAM, Leu-Rch Rep, and Reelin, is discussed. The 7q31 breakpoint interval has also been implicated in other neuropsychiatric diseases that demonstrate some clinical overlap with GTS, including autism and speech-language disorder.
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PMID:Disruption of a novel gene (IMMP2L) by a breakpoint in 7q31 associated with Tourette syndrome. 1125 43

Hyper-IgE syndrome with recurrent infections (HIES) is a primary immunodeficiency disease characterized by recurrent skin and lung abscesses and extreme elevations of serum IgE, but also involving dentition, bones, and connective tissue. Although the etiology of HIES is unknown, autosomal dominant inheritance has been observed in multiple kindreds. A 17 year old male with sporadic HIES, autism, and mild mental retardation was found to have a supernumerary marker chromosome in peripheral blood lymphocytes and skin fibroblasts. Microdissection and FISH analysis of the marker chromosome showed that it was derived from a small interstitial deletion of one homologue of chromosome 4q21. Lack of hybridization of probes specific for telomeres and alphoid centromeres, including a centromere 4 specific probe, established that the marker was an analphoid ring chromosome. Comparative genotyping of transformed B-cell subclones with (M+) and without (M-) the marker chromosome showed loss of the maternal alleles in M- cells between markers D4S1569 and D4S3010. FISH using YAC clones from 4q21 confirmed the size and location of the interstitial deletion. Thus our patient's phenotypes were associated with de novo formation of a marker chromosome containing 15-20 cM of DNA deleted from his maternally derived chromosome 4. Proximal chromosome 4q therefore is a candidate region for disease genes for both HIES and autism. Identification of genes disrupted or lost during the formation of the marker chromosome as well as linkage studies in kindreds with HIES or autism may help us to understand the etiology of these complex phenotypes.
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PMID:Analphoid marker chromosome in a patient with hyper-IgE syndrome, autism, and mild mental retardation. 1125 75

Autistic disorder (MIM 209850) is currently viewed as a neurodevelopmental disease. Reelin plays a pivotal role in the development of laminar structures including the cerebral cortex, hippocampus, cerebellum and of several brainstem nuclei. Neuroanatomical evidence is consistent with Reelin involvement in autistic disorder. In this study, we describe several polymorphisms identified using RNA-SSCP and DNA sequencing. Association and linkage were assessed comparing 95 Italian patients to 186 ethnically-matched controls, and using the transmission/disequilibrium test and haplotype-based haplotype relative risk in 172 complete trios from 165 families collected in Italy and in the USA. Both case-control and family-based analyses yield a significant association between autistic disorder and a polymorphic GGC repeat located immediately 5' of the reelin gene (RELN) ATG initiator codon, as well as with specific haplotypes formed by this polymorphism with two single-base substitutions located in a splice junction in exon 6 and within exon 50. Triplet repeats located in 5' untranslated regions (5'UTRs) are indicative of strong transcriptional regulation. Our findings suggest that longer triplet repeats in the 5'UTR of the RELN gene confer vulnerability to autistic disorder.
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PMID:Reelin gene alleles and haplotypes as a factor predisposing to autistic disorder. 1131 13


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