ISSN:1080-4013    

DOI:10.1002/mrdd.1410010402

出版商:John Wiley&Sons, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractFragile X syndrome, the leading known inherited cause of mental retardation and developmental disabilities, is caused by a trinucleotide repeat expansion in the 5′ untranslated region of the FMR1 gene in Xq27.3 Research during the pat five years has documented the genetic abnormalities that cause this syndrome and described the impairments, disabilities, and disadvantages asslociated with it. Future research is needed to foucs on genetics and neurobiology, screening and early identification, biomedical treatments, psychoeducational interventions, and family adaptation and support. © 1995 Wiley‐Liss,

ISSN:1080-4013    

DOI:10.1002/mrdd.1410010403

出版商:John Wiley&Sons, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractFragile X syndrome results from a massive trinucleotide repeat expansion in the 5′ untranslated region of the gene FMR1. Methylation of FMR1 occurs as a result of this expansion, causing transcriptional silencing. Therefore, the absence of FMR protein (FMRP) appears to result in fragile X syndrome. Characterization of the gene and its expression, as well as the cellular localization and functional properties of the protein, provide insight into how the absence of FMRP results in mental retardation and the related phenotype. Alternative splicing of FMR1 transcripts leads to protein isoforms and suggests that this cell is functionally diverse. Among vertebrates, FMRP is highly conserved at the amino acid level and localizes mainly to the cytoplasm. The presence of two protein sequence motifs, the RGG box and the KH domain, suggests that FMRP is an RNA‐binding protein. Direct experimentation shows that FMRP is capable of binding its own RNA in vitro, as well as a subset of brain‐derived messages. Further understanding of how these interactions take place and identification of those genes having messages that interact will provide insight into the mechanisms of cognitive function in humans. © 1995 Wiley‐L

ISSN:1080-4013    

DOI:10.1002/mrdd.1410010404

出版商:John Wiley&Sons, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractFragile X syndrome, the most common cause of inherited mental retardation, is the result of unstable expansions of a CGG repeat located in the 5′ untranslated region of the FMR1 gene. Normal alleles consist of 6‐50 CGG repeats, in general interspersed by 1–3 AGGs. Moderate expansions up to 200 repeats, called premutations, are found in phenotypically normal carrier males or females. When transmitted by a female, a premutation has a risk of up to 100% of further expansion to an abnormally methylated full mutation (230 to>1,000 CGGs), which results in shut‐down of FMR1 expression. In contrast, affected males with a full mutation carry a premutation in their sperm that is transmitted to their daughters. On maternal transmission, the timing of the transition from premutation to full mutation remains unsolved. It is generally believed, but has not been proven that this is a postzygotic event, in which case an imprinting mechanism is required to distinguish a premutation carried on a maternal or paternal X chromosome. As in other trinucleotide expansion diseases, linkage disequilibrium between the fragile X mutations and haplotypes of adjacent polymorphisms has been found in various populations, indicating founder effects. These studies have suggested that normal alleles that carry long perfect CGG repeats may constitute alleles that are predisposed to multistep expansion over many generations. The ability to detect the various types of mutations has revolutionized the diagnosis of the disease and genetic counseling, and should allow more precise estimates of the population frequency of the fragile X syndrome. It may also allow screening for carrier females in the general population. We discuss possible mechanisms of expansion in light of the unusual structural properties proposed for CGG repeats. Various other folate‐sensitive fragile sites that are also caused by unstable expansions of CGG (CCG) repeats are being cloned and characterized. In particular, methylated expansions at the FRAXE locus appear to be associated with mild mental retardation. © 1995 Wiley

ISSN:1080-4013    

DOI:10.1002/mrdd.1410010405

出版商:John Wiley&Sons, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractElucidation of the nature of the mutational process that leads to fragile X syndrome and other triplet repeat disorders poses an interesting problem. At present, no experimental model systems are available to study the expansion process. Moreover, data from fragile X family studies reveal only the behavior of the highly expanded form of the mutation. Thus, mathematical modeling of the mutational process has become an important tool for use in examining the nature and fate of the fragile X gene. Such methods can be used to generate predictions that can be tested using empirical data. This article reviews these models and discusses the predicted allele frequencies at equilibrium and the approach to equilibrium. © 1995 Wiley‐Liss, I

ISSN:1080-4013    

DOI:10.1002/mrdd.1410010406

出版商:John Wiley&Sons, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractFragile X syndrome, the leading known cause of heritable mental retardation, is associated with mutations of the FMR1 gene on the X chromosome. Neurobiological research has characterized several gene‐brain‐function correlations in fragile X syndrome, although no complete pathogenic mechanisms have yet been elucidated. This report summarizes current knowledge of the neurobiology of fragile X syndrome. Published research findings are presented along with a discussion of the relevance of neurobiological data to the neurobehavioral phenotype and genetic mechanisms associated with the FMR1 mutation. © 1995 Wiley‐Lis

ISSN:1080-4013    

DOI:10.1002/mrdd.1410010407

出版商:John Wiley&Sons, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractSince the advent of DNA testing after 1991, variations in molecular patterns, such as the CGG expansion length, mosaicism, partial methylation, and X‐inactivation, have been correlated with the degree of phenotypic involvement in fragile X syndrome. Although some reports conflict it appears that a low CGG repeat number within the full mutation range or lack of methylation, whether almost complete or partial, is associated with only mild involvement in males. A subgroup of individuals with the premutation may also demonstrate mild problems associated with fragile X syndrome. This article reviews preliminary studies of FMRP expression and discusses a hypothesized correlation between FMRP expression and phenotypic involvement. Molecular and clinical correlations are advancing our understanding of the mild range of phenotypic involvement in fragile X syndrome, which involves learing disabilities and emotional difficulties, but not mental retardation. © 1995 Wiley‐Liss,

ISSN:1080-4013    

DOI:10.1002/mrdd.1410010408

出版商:John Wiley&Sons, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractAdaptive behavior has long been a key component of the definition of mental retardation. However, research on these important skills in fragile X and other genetic syndromes is just under way, having taken a back seat to studies using mixed etiologic groups. Further, adaptive behavior is complex, and measurements of these skills must have a developmental orientation, apply to multiple life settings, and reflect typical as opposed to optimal performance. After reviewing these features, this article highlights three areas of adaptive functioning in males with fragile X syndrome: profiles, trajectories, and adaptive behavior‐IQ relations. Many males with fragile X show relative strengths in domestic and personal chores of daily living, or so‐called “practical” intelligence. Whereas age‐related gains in adaptive skills are often seen in boys, particularly during the preschool years, adolescents and adults seem to have relative stable adaptive age scores and declines in adaptive standard scores. Such developmental courses may parallel the IQ trajectory often seen in males with fragile X syndrome. The need for further adaptive research is emphasized, particularly in light of the critical role these skills play in the ultimate life success of individuals with mental retardation. © 1995 Wiley

ISSN:1080-4013    

DOI:10.1002/mrdd.1410010409

出版商:John Wiley&Sons, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractFragile X syndrome, the most common form of inherited mental retardation, is associated with a broad spectrum of cognitive and behavioral impairments. Researchers have noted a characteristic behavioral profile consisting of social avoidance, as well as verbal and motor repetitive behaviors, in a subgroup of males with fragile X syndrome. Although these behaviors are evident in their most extreme form in males having both fragile X syndrome and autism, milder variants are evident in nonautistic males as well. Clinical data we have collected suggest that the severity of these agitated behaviors starts increasing during adolescence. These data suggest fragile X males have problems with arousal modulation. It is hypothesized that these arousal problems have an impact on both the acquisition and display of cognitive and adaptive skills. Neurocomputational issues that may be relevant to understanding these cognitive and emotional phenomena are discussed. © 1995 Wiley‐Liss, I

ISSN:1080-4013    

DOI:10.1002/mrdd.1410010410

出版商:John Wiley&Sons, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractIn 1980, Turner et al. described a sample of females affected with fragile X syndrome and recommended that all females with mental retardation of unknown etiology be evaluated for this condition. Since then, much has been learned about fragile X syndrome and its effects on females. Although research has primarily focused on abnormal cognitive and emotional findings in a proportion of women, studies have also addressed the physical characteristics and specific findings of young girls. Some of the early results were puzzling because so little was understood about the genetics of this condition, but much has become clear since the gene was sequenced in 1991. Many questions about this condition are still unanswered, but are likely to be addressed in the near future. This article highlights major advances made during the past 10 years with regard to females having fragile X syndrome. © 1995 Wiley‐Liss, I

ISSN:1080-4013    

DOI:10.1002/mrdd.1410010411

出版商:John Wiley&Sons, Inc.    

年代:1995

数据来源: WILEY