Mental status of females with an FMR1 gene full mutation.

The cloning of the FMR1 gene enables molecular diagnosis in patients and in carriers (male and female) of this X-linked mental retardation disorder. Unlike most X-linked disorders, a considerable proportion of the female carriers of a full mutation of the FMR1 gene is affected. In this study, the intelligence quotients (IQs) were ascertained by the Wechsler Adult Intelligence Scale in 33 adult females with a full mutation, with 28 first-degree adult female relatives (mainly sisters) without a full mutation as controls. Seventy-one percent of the females with a full mutation had IQ scores below 85. In paired analysis, no significant correlation could be detected between the IQs of the females with a full mutation and those of their first-degree female relatives, reflecting a dominant effect of the FMR1 gene full mutation in the mental development of females. Considering females with a full mutation only, we observed a significant relation between the proportion of normal FMR1 alleles on the active X chromosome and IQ. We present a model to explain this relationship.

A deletion of 1.6 Kb proximal to the CGG repeat of the FMR1 gene causes fragile X-like psychological features.

In this report we present the results of psychological investigations in a family in which 11 individuals, 7 females and 4 males, have a deletion of 1.6 Kb proximal to the CGG repeat of the FMR1. All 4 males with the deletion and 2 of the female carriers show characteristics of the fragile X clinical and behavioural phenotype. The findings in the present family illustrate that the typical characteristics of the fragile X syndrome can be caused by other types of mutations involving the FMR1 than the highly expanded stretches of CGG repeats in the 5' noncoding region of the FMR1 gene, coinciding with abnormal methylation patterns in that area as present in the vast majority of individuals with the fragile X syndrome.

Adaptive behavior in the fragile X syndrome: profile and development.

In this study we present data on the adaptive behavior profile and on the development of adaptive functioning in 39 fragile X [fra(X)] males, age 4-26 years. Social adaptability is relatively well developed as compared to cognitive level and especially self-help skills continue to grow with age despite a stagnation in intellectual growth.

Mental status and fragile X expression in relation to FMR-1 gene mutation.

The fragile X mental retardation syndrome is caused by unstable expansion of a CGG repeat in the FMR-1 gene. Clinical expression is associated with a large expansion of the CGG repeat. The mutation in the FMR-1 gene and the cytogenetic expression of the fragile site at Xq27.3 have been studied in 52 fragile X male patients. The percentage of the cytogenetic expression of the fragile site at Xq27.3 positively correlates with the mean size of the full mutation in the FMR-1 gene (p < 0.0001) irrespective of the presence of additional premutation alleles. We noted a less frequent occurrence of additional premutation alleles in adult patients compared with juveniles, suggesting a continued mitotic instability in life. Additionally, the level of mental retardation has been ascertained in 35 patients using the Stanford-Binet or Terman-Merrill test of general intelligence. The presence of a full mutation in the FMR-1 gene seemed decisive for the occurrence of mental impairment in the patient. No correlation is observed between the degree of mental retardation and the size of the full mutation. The degree of mental retardation seemed not to be influenced by the presence of premutation alleles in part of the cells in addition to a full mutation. One patient is described with the 'Prader-Willi-like' subphenotype of the fragile X syndrome, showing a deletion in the FMR-1 gene in a part of his cells in addition to a full mutation.

Strengths and weaknesses in the cognitive profile of youngsters with Prader-Willi syndrome.

In this report we present the results of a study of the intellectual functioning and cognitive profile of 26 Prader-Willi syndrome (PWS) patients. The mean IQ score was 62.3 (range 39-96). In 13 patients a significant difference between verbal and performance IQ was found. In 10 of them the performance IQ was higher than the verbal. The results of subtest analysis indicate that cognitive strengths are more visible than cognitive weaknesses. Highest scores were noted especially in the performance scale, i.e. Block Design (9 children) and Coding or Mazes (5 children). Analysis of all available data indicates that PWS patients score better on visual motor discrimination skills than on auditory verbal processing skills. These results are promising for intervention programs and education strategies.

A survey of cattle for antibodies against bluetongue and epizootic hemorrhagic disease of deer viruses in British Columbia and southwestern Alberta in 1987.

In 1987 a serological survey of cattle for antibodies (Ab) to bluetongue virus (BTV) and epizootic hemorrhagic disease virus (EHDV) was undertaken in British Columbia and southwestern Alberta after infection with the viruses was diagnosed in wild and domestic ruminants in the Okanagan Valley. Of 4610 cattle tested, five had Ab only to BTV, 125 had antibodies only to EHDV and 16 had Ab to both viruses. The Ab were identified as specific for BTV type 11 (BT-11) or EHDV type 2 (EHDV-2). All but one of the seropositive cattle originated in the Okanagan Valley of British Columbia. The remaining one seropositive animal which had Ab to EHDV-2 was pastured with a bull purchased from the Okanagan Valley.

Intelligence and the fra(X) syndrome: a review.

In this paper we review the data on intelligence in fra(X) males reported up to now in the literature, with special attention to its evolution with age. The available data suggest a decline in intellectual functioning in relation to age. These findings, however, should be interpreted with caution because of sampling and other methodological problems related with the fra(X) screening procedures and programs in general.

The 49,XXXXY syndrome: clinical and psychological findings in five patients.

In this study clinical and psychological findings are presented in five 49,XXXXY patients. Their degree of mental retardation varied greatly, i.e. from moderately to profoundly retarded. A decline in intelligence performance with age was observed in one boy. Language development was severely retarded with a remarkable discrepancy between language expression and comprehension. Emotional disturbances with low frustration level, timidity and shyness were noted in all five and their level of adaptive functioning was much higher than the cognitive level.

Strengths and weaknesses in the cognitive profile of fra(X) patients.

In this paper we present data on the cognitive abilities analyzed by systematic, standardized psychometric testing in 18 fra(X) boys who participated in a multicenter, longitudinal study. In the majority of the patients no significant differences were found between verbal and performance intelligence. Higher performance IQ than verbal IQ was found primarily in higher functioning fra(X) males, indicating a possible effect of level of functioning on the direction of verbal-performance IQ differences. Subtest-analyses showed lowest performances in Number Concept and Arithmetic Skills, whereas better performances were reached in Object Assembly and Picture Completion. These data are discussed and compared with the results in previous studies reported up to now.

Adaptive behavior in the fra(X) syndrome: a longitudinal study in eight patients.

In this study we investigated the development of adaptive behavior of 8 fragile X [fra(X)] males with special attention to social competence and compared the results with a control group of 8 fra(X) negative males matched for age, level of adaptive functioning, and period of institutionalization.

Intelligence and cognitive profile in the fra(X) syndrome: a longitudinal study in 18 fra(X) boys.

A longitudinal study of IQ and cognitive profile in 18 fra(X) positive boys is reported. At the time of diagnosis, four of the boys were mildly retarded, seven were moderately retarded, and five were severely mentally retarded. Intelligence was borderline in one child and normal in another. A decline in intellectual performance with age in the fra(X) syndrome indicated in previous studies was not confirmed and we review the reported data on this subject.

A systematic cytogenetic study of a population of 1170 mentally retarded and/or behaviourly disturbed patients including fragile X-screening. The Hondsberg experience.

A cytogenetic study was performed in a population of 1170 mentally retarded and/or behaviourly disturbed patients of the Hondsberg Institute in the south of the Netherlands. The cytogenetic data are presented and discussed. In all patients chromosomal evaluation was performed with Giemsa-banding and Quinacrine fluorescence, and additional banding techniques were performed whenever they were necessary to clarify the chromosomal abnormality. A fragile X screening with M199 cultures was performed in 311 males. In 22.1% of the patients a chromosomal basis was found for their developmental retardation: 14.3% Down syndrome patients, 6.1% other chromosomal abnormalities (mainly partial autosomal trisomies and monosomies and sex-chromosome abnormalities). In 24 males, through 21 index patients, a positive fragile X screening was found, i.e. 6.7% of the screened population and 1.8% of the total population. These results indicate that the diagnostic contribution of the fragile X screening is numerically of equal importance as are advanced chromosome banding techniques, and its contribution to the diagnosis of fragile X syndrome in one index male patient in general leads to the detection of several female relatives at risk to be carrier of this X-linked recessively inherited condition. The causal relationship between the occurrence of mental retardation and chromosomal aberration in genera i.e. autosomal trisomies, partial autosomal trisomies and monosomies, and Xq27-28 fragility is well established and is, to some extent, easy to understand. Whether carriers of other chromosomal rearrangements, mainly of balanced reciprocal and Robertsonian translocations, small extra chromosomes, paracentric inversions and chromosomal variants, have increased risk for mental handicap and/or congenital malformations in their progeny, remains unclear at the present time. Some of these residual problems and questions are discussed in the perspective of their importance for genetic counseling. Detailed data will be presented about the mental development and psychological profile of patients with these different types of chromosomal abnormalities and rearrangements.