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)

Autism is a rare neurodevelopmental disorder with a strong genetic component. Co-occurrence of autism and chromosomal abnormalities is useful to localize candidate regions that may include gene(s) implicated in autism determinism. Several candidate chromosomal regions are known, but association of chromosome 22 abnormalities with autism is unusual. We report a child with autistic syndrome and a de novo 22q13.3 cryptic deletion detected by FISH. Previously described cases with 22q13.3 deletions shared characteristic developmental and speech delay, but autism was not specifically reported. This case emphasizes a new candidate region that may bear a gene involved in autism etiopathogenesis. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:839-844, 2000.
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PMID:Case with autistic syndrome and chromosome 22q13.3 deletion detected by FISH. 1112 Nov 93

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

We report a de novo, apparently balanced (2;8)(q35;q21.2) translocation in a boy with developmental delay and autism. Cross species (colour) paint (Rx) and SKY FISH, forward and reverse chromosome painting, and FISH with subtelomeric probes were used to examine the patient's karyotype, but further rearrangements were not detected. FISH with region specific clones mapping near 2q35 and 8q21.2 breakpoints and STS mapping performed on the isolated derivative chromosomes were used to refine the location of the breakpoints further. A cryptic deletion of between 4.23 and 4.41 Mb in extent and involving at least 13 complete genes or transcription units was found at the breakpoint on 2q35. The deletion includes the promoter and 5' untranslated region of the paired box 3 (PAX3) gene. The child has very mild dystopia canthorum which may be associated with the PAX3 haploinsufficiency. The 8q21.2 breakpoint is within MMP16 which encodes matrix metalloproteinase 16. We postulate that the cryptic deletion and rearrangement are responsible for the patient's phenotype and that a gene (or genes) responsible for autism lies at 2q35 or 8q21.2. The results present a step towards identifying genes predisposing to autism.
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PMID:A cryptic deletion of 2q35 including part of the PAX3 gene detected by breakpoint mapping in a child with autism and a de novo 2;8 translocation. 1207 Feb 44

15q11- q13 contains many imprinted genes, and undergoes duplicon-mediated rearrangements, including deletions, duplications and triplications, and generation of marker chromosomes. Abnormal phenotypes, including language delays and autism spectrum disorders, are primarily observed with maternal 15q11- q13 duplication. To determine possible epigenetic effects on expression within duplicated 15q11- q13 regions, we utilized RNA-FISH to directly observe gene expression. RNA-FISH, unlike RT-PCR, is polymorphism-independent, and it also detects relative levels of expression at each allele. Unamplified, gene-specific RNA signals were detected using cDNA probes. Subsequent DNA-FISH confirmed RNA signals and assigned parental origin by colocalization of genomic probes. SNRPN and NDN expression was detected primarily from paternal alleles. Control Dystrobrevin transcripts were detected equally from both alleles; however, maternal-UBE3A signals were consistently larger than paternal signals in normal fibroblasts and in neural-precursor cells. Larger UBE3A signals were also observed on one or both maternal alleles in a cell line carrying a maternal interstitial duplication, on both alleles of a maternally derived marker(15) chromosome, and occasionally on a paternal allele in a cell line carrying a paternal interstitial duplication. Expression of NDNL2, just distal to the duplicated region, was not markedly altered but paralleled changes in UBE3A expression. Excess total maternal-UBE3A RNA was confirmed by Northern blot analysis of cell lines carrying 15q11- q13 duplications or triplications. These results demonstrate that: (1) UBE3A is imprinted in fibroblasts, lymphoblasts and neural-precursor cells; (2) allelic imprint status is maintained in the majority of cells upon duplication both in cis and in trans; and (3) alleles on specific types of duplications may exhibit an increase in expression levels/loss of expression constraints.
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PMID:Allele-specific expression analysis by RNA-FISH demonstrates preferential maternal expression of UBE3A and imprint maintenance within 15q11- q13 duplications. 1209 13

To assess the frequency of cytogenetic abnormalities in children with autism spectrum disorders (ASDs), routine G-banded cytogenetic analyses and FISH studies to rule out 15q11.2 and 17p11.2 duplications were performed on 49 children with ASDs. Blood samples were further studied using a complete set of subtelomeric FISH probes. Routine chromosome study showed that one child had a small duplication of chromosome 5: 46,XY,dup(5)(p?14.2p?15.1). Another child had an interstitial duplication of the Prader-Willi and Angelman syndrome critical region of chromosome 15, detected by FISH analysis. The detection of these two cases underscores the importance of obtaining routine chromosome and 15q11-q13 FISH analyses in children with ASDs. No instance of 17p11.2 duplication was observed. Subtelomeric analysis did not reveal abnormalities in any of the subjects.
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PMID:Routine cytogenetic and FISH studies for 17p11/15q11 duplications and subtelomeric rearrangement studies in children with autism spectrum disorders. 1256 5

In this report we describe the case of an 11-year-old male with autism and mental retardation, presenting a tetrasomy of chromosome 3q. Cytogenetic analysis showed a mosaic for an unbalanced karyotype consisting of mos46,XY,add(12)(p13.3)(56)/46,XY(45). FISH using WCP and subtelomeric probes identified the extra material on 12p to be an inverted duplication of the distal segment of chromosome 3q. Anomalies in chromosome 3q have not been previously described in association with autism, although association with psychomotor delays and behavior problems has been frequently reported and are here further discussed. This chromosomal 3q segment is therefore likely to include genes involved in specific neurodevelopment pathways, and further analysis of the region is warranted for the identification of the molecular alterations that lead to the autistic features described.
J Autism Dev Disord 2003 Apr
PMID:Partial tetrasomy of chromosome 3q and mosaicism in a child with autism. 1275 57

We present a 6-year-old boy with moderate developmental delay, gait disturbance, autism related disorder and mild dysmorphic features. He was seen for evaluation of his retardation since the age of 2.8 years. At first sight, a cytogenetic analysis showed a normal 46,XY karyotype. Neurological examination at the age of 5.5 years revealed a motor and sensory polyneuropathy. A quantitative Southern blot with probes PMP22 and VAW409 specific for Charcot-Marie-Tooth type 1 (CMT1) disclosed a duplication which confirmed the diagnosis HMSN Ia. Subsequently, GTG banded metaphases were re-evaluated and a small duplication 17p was seen on retrospect. Additional FISH with probe LSISMS (Vysis) specific for the Smith-Magenis region at 17p11.2 again showed a duplication. Both parents had a normal karyotype and the duplication test for CMT1 showed normal results for both of them. The boy had a de novo 46,XY,dup(17)(p11.2p12) karyotype. The present observation confirms previous findings of mild psychomotor delay, neurobehavioural features and minor craniofacial anomalies as the major phenotypic features of dup(17)(p11.2) and dup(17)(p11.2p12); in cases of duplications comprising the PMP22 locus HMSN1 is associated. A recognizable facial phenotype emerges characterized by a broad forehead, hypertelorism, downslant of palpebral fissures, smooth philtrum, thin upper lip and ear anomalies.
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PMID:Hereditary motor and sensory neuropathy (HMSN) IA, developmental delay and autism related disorder in a boy with duplication (17)(p11.2p12). 1508 3

Chromosome 10p terminal deletions have been associated with a DiGeorge like phenotype. Haploinsufficiency of the region 10p14-pter, results in hypoparathyroidism, sensorineural deafness, renal anomaly, that is the triad that features the HDR syndrome. Van Esch (2000) identified in a HDR patient, within a 200 kb critical region, the GATA3 gene, a transcription factor involved in the embryonic development of the parathyroids, auditory system and kidneys. We describe a new male patient, 33-year-old, with 10p partial deletion affected by hypocalcemia, basal ganglia calcifications and a severe autistic syndrome associated with mental retardation. Neurologically he presented severe impairment of language, hypotonia, clumsiness and a postural dystonic attitude. A peripheral involvement of auditory pathways was documented by auditory evoked potentials alterations. CT scan documented basal ganglia calcifications. Hyperintensity of the lentiform nuclei was evident at the MRI examination. Renal ultrasound scan was normal. Haploinsufficiency for GATA3 gene was documented with FISH analysis using cosmid clone 1.2. Phenotypic spectrum observed in del (10p) is more severe than the classical DGS spectrum. GATA3 has been found to regulate the development of serotoninergic neurons. A serotoninergic dysfunction may be linked with autism in this patient.
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PMID:Chromosome 10p deletion in a patient with hypoparathyroidism, severe mental retardation, autism and basal ganglia calcifications. 1533 74

The chromosome region 15q11q13 is known for its instability, and many rearrangements may occur in this imprinted segment: deletions associated either with Angelman syndrome (AS) or with Prader-Willi syndrome (PWS), according to parental origin; translocations; inversions; and supernumerary marker chromosomes formed by the inverted duplication of proximal chromosome 15. Inv dup(15) constitute the most common of the heterogeneous group of the extra structurally abnormal chromosomes, and their presence results in tetrasomy 15p and partial tetrasomy 15q. Inv dup(15), containing the Prader-Willi/Angelman syndrome region, are associated with altered behaviour, developmental delay/mental retardation, and seizures/epilepsy. Clinicians should suspect this syndrome in any infant/child with early central hypotonia, minor dysmorphic features, developmental delay, autism or autistic-like behaviour, and who subsequently develops hard to control seizures/epilepsy. Diagnosis is confirmed by standard cytogenetic techniques and FISH analysis. Although, about 100 cases have been reported to date, limited data are available on the natural history. To obtain better information on diagnosis and outcome in a clinical setting, we reviewed the available literature on clinical and behavioural phenotype of inv dup(15) syndrome.
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PMID:The inv dup(15) or idic(15) syndrome: a clinically recognisable neurogenetic disorder. 1602 54


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