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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Standardized cognitive, behavioral, and neuroanatomical data are presented on 2 unrelated boys with the FRAXE (FMR2) GCC expansion mutation. In the context of normal IQ, both boys had a history of developmental delay, including significant problems with communication, attention, and overactivity. Additionally, one child was diagnosed with autistic disorder. Data from these 2 cases are compared to analogous information from previous reports about individuals with the FRAXE or FRAXA (FMR1) mutation. These comparisons support the idea that FRAXE is associated with nonspecific developmental delay and possibly high-functioning autism.
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PMID:Cognitive, behavioral, and neuroanatomical assessment of two unrelated male children expressing FRAXE. 903 11

Unstable (CAG)n trinucleotide repeat microsatellites are hypothesized to cause schizophrenia. The (CAG)n microsatellite of dominant spinal cerebellar ataxia type 1 (SCA1) is a candidate schizophrenia gene. Autism results from expansions of (CGG)n and (GAA)n trinucleotide repeat stretches at fragile X syndrome (FRAXA), and the recessive Friedreich's ataxia (FA). Dominant ataxia genes may cause schizophrenia and recessive ataxia genes may cause autism. Syndromes with autism show purine synthesis defects (PSDs) and/or pigmentation defects (PDs). Autism is caused by very lengthy expansions of (CAG)n, (CGG)n and (GAA)n repeats, while schizophrenia results from much smaller (CAG)n and (CGG)n repeat expansions.
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PMID:Expanded (CAG)n, (CGG)n and (GAA)n trinucleotide repeat microsatellites, and mutant purine synthesis and pigmentation genes cause schizophrenia and autism. 979

The present paper addresses post mortem pathological and neuropathological findings in two males with fragile-X syndrome, aged 67 and 87 years. Both subjects died from sudden, unexpected cardiovascular causes, and both showed abnormalities of the mitral valve, ventricular hypertrophy and cardiomegaly. Both cases demonstrated macrocephaly characteristic of the classical Martin-Bell phenotype in FRAXA. There was increased brain weight in both cases: macroscopically, both cerebral and cerebellar hemispheres appeared normal, but dilated lateral ventricles were seen; and microscopic examination of the brain in case 2 showed normal hexalaminar architecture and no gross neuronal dropout. The hippocampus showed mild CA4 pyramidal cell loss and associated gliosis. The cerebellum showed focal Purkinje cell loss and corresponding Bergmann gliosis. Whilst there is a need to delineate the microscopic features of fragile-X syndrome from those of the ageing process, there is an urgent need for more systematic neuropathological studies of fragile-X syndrome; the increased brain weight and Purkinje cell loss in autism and fragile-X syndrome reopens the debate on these two conditions. The case for further research into the cardiac anomalies in fragile-X syndrome is also strengthened by the findings. Finally, the present report confirms the role of interstitial cell hyperplasia as the major cause of megalo-testes in this condition.
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PMID:Pathological and neuropathological findings in two males with fragile-X syndrome. 1071 53

In summary, autism genetics has moved from a time of identification of heritability and determination of risk of "lesser variants" or the "broader phenotype" in relatives to a phase where some cases of autism have a definite basis such as maternally inherited duplications of 15q11-q13, identification of mutations causing AS, Rett syndrome, and FRAXA. The first phase of genome-wide screens has not revealed definitive linkage, but as samples are enlarged and meta-analyses performed, the strongest linkage findings are likely to yield susceptibility variants once fine mapping proceeds. Recent statistical and molecular genetic analysis methods make the additional work feasible. However, frustrating it may be to be in this phase of the research, it is an essential part of the process of moving from identification of heritability in autism to understanding of the disorder in a way that may permit improved treatment in the future. If there is an advantage to autism being a complex rather than monogenic disorder, it is that the nature of multiplicative or interacting genetic risk is that prevention or treatment directed to any of the identified genetic risks may be sufficient to break a chain of pathophysiology. More genes increase the chance that one or more will have implications for treatment development sooner.
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PMID:Genetics of autism. 1135 2

Studies of the relationship between the fragile X (FRAXA) mutation and autism have been controversial. Although there are differences between the two populations, individuals with FRAXA and autism exhibit remarkably similar aberrant behavior patterns. We examined comparably aged children and adolescents with FRAXA or autism to determine whether longitudinal changes in cognitive ability and adaptive behavior were similar in the two groups. We found decreases in IQ scores in young children with FRAXA as well as in those with autism. Declines in IQ scores were steeper among children with FRAXA. Older children and adolescents with autism exhibit stable test-retest scores, whereas older children with FRAXA continue to show decreases. Comparable declines in adaptive behavior composite scores were observed in both groups, at all ages tested, and across all adaptive behavior domains.
J Autism Dev Disord 2002 Apr
PMID:Longitudinal changes in cognitive and adaptive behavior scores in children and adolescents with the fragile X mutation or autism. 1145 Aug 26

With the aim of analyzing which complementary tests are relevant in the diagnostic evaluation of individuals with pervasive developmental disorders, a protocol of clinical and laboratory evaluation was applied in 103 outpatients. The protocol included chromosomal analysis, screening for inborn errors of metabolism, cytogenetic and molecular study of the FRAXA, FRAXE, and FRAXF mutations, EEG, SPECT, and magnetic resonance imaging study. Eighty-four subjects concluded the complementary tests and were classified either as having autism, atypical autism or Asperger syndrome according to the DSM-IV criteria. Sixteen individuals, all bellonging to the two autistic groups, presented genetic or enviromental factors that may have lead to the behavioral disorders, showing the importance of diagnostic evaluation in this group of conditions. Neuroimaging and EEG findings were non-specific and occurred in similar proportion among the groups, being considered of relative low significance in the diagnostic evaluation of individuals with pervasive developmental disorders.
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PMID:Genetic and neurological evaluation in a sample of individuals with pervasive developmental disorders. 1280 92

Fragile X syndrome is a frequent genetic disease associated to developmental disorders, including learning disability, mental retardation, behavioral problems and pervasive developmental disorders (autism and related conditions). We studied a sample of 82 individuals (69 males and 13 females) presenting with pervasive developmental disorders using three techniques for the diagnosis of fragile X syndrome (FXS). Cytogenetic analysis detected the fragile site in four males, but only one showed a consistent positive rate. Molecular study based on the PCR technique was inconclusive for most females (92.3%), which where latter submitted to Southern blotting analysis, and for one male (1.4%), excluding the FRAXA mutation in the remaining male individuals (98.6%). Molecular tests using the Southern blotting technique confirmed only one positive case (1.2%) in a male subject. These results showed that Southern blotting analysis of the FRAXA mutation has the best sensitivity and specificity for the diagnosis of FXS but also validated the PCR technique as a confinable screening test.
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PMID:Laboratorial diagnosis of fragile-X syndrome: experience in a sample of individuals with pervasive developmental disorders. 1617 1

In a prospective study in Kuwait, 182 mentally retarded male patients who fulfilled 5 or more clinical criteria of fragile X syndrome were screened using polymerase chain reaction (PCR) testing. Twenty patients (11%) were highly suspected of having fragile X syndrome due to mutation at the FRAXA locus; none had mutation at the FRAXE locus. Of these, 11 (55%) were confirmed fragile-X-positive by both cytogenetic and PCR techniques. The most frequent clinical features were: prominent forehead, high arched palate, hyperextensible joints, long ears, prominent jaw, height > 10th centile and attention-deficit hyperactivity. Less common were avoidance of eye contact (45%), autism (45%) and seizures (30%). Large testes were found in 55% of cases. Pre-pubertal and post-pubertal clinical criteria were different.
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PMID:Fragile X syndrome: a clinico-genetic study of mentally retarded patients in Kuwait. 1620 16

The high concordance for autism symptoms in monozygotic twin-pairs compared to di-zygotic twins and/or non-twin sib-ships suggests a high genetic determinism in autism. Those results have hypothesized multi-factorial determinism in accordance with family studies and mathematical models. However, linkage and association or candidate gene strategies have failed to-date to identify clearly involved mechanisms. Mental retardation (MR) is known as frequently associated to autism. Multiplex XLMR pedigrees have been reported with only one mutated patient having autism and MR: different X-located MR genes have been shown to be involved (NLGN4, MECP2, OPHN1, ZNF674 and FRAXA) which does not suggest that they could be "autism genes". Tuberous sclerosis studies and report of numerous autosomal domains shown deleted in MR-autistic subjects suggest that several autosomal dominant (AD) genes could be also involved in MR with autism. Whereas multiplex AD-MR families are rare, AD de novo mutations could explain numerous sporadic situations of non-specific MR and of autism with MR, in accordance with twin studies. Finally, we hypothesize that in those autistic subjects with mendelian MR, the XL-MR or AD-MR gene (G1) would pave the way for a second Mendelian factor (G2) responsible for autism symptoms.
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PMID:Could autism with mental retardation result from digenism and frequent de novo mutations? 1916 Jan 28

Autism is a strong genetic disorder, with an estimated heritability greater than 90%. Nonetheless, its specific genetic aetiology remains largely unknown. Autism is associated with epilepsy in early childhood and epilepsy occurs in 10-30% of individuals with autism. Here we report the case of a woman affected by a severe epileptic disorder with an onset at 14 years old. She is affected by a cryptogenetic focal epilepsy with complex partial (psychomotor) and secondarily generalized tonic-clonic seizures, which are drug resistant. The woman is married to a healthy man and has six children: two girls are healthy, a girl and two boys are affected by autism while one boy shows partial seizures. The three children with autism show moderate mental retardation and an EEG with no epileptiform alterations. The child with epileptic seizures shows an asymmetric EEG that is not necessarily pathological. In this family, no chromosomal rearrangements were detected by means of classical cytogenetic analyses. The presence of FRAXA alterations and of microdeletions of the 15q11-q13 chromosome region were also excluded. A genome-wide linkage analysis using microsatellite markers revealed several chromosome regions as possible susceptibility loci.
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PMID:Clinical and genetic evaluation of a family showing both autism and epilepsy. 2015 87


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