The frequency of X-linked mental retardation

600 mentally retarded children, 339 boys and 261 girls aged 5-9 years were examined. Boys to girls ratio (B:G) was found in the total group to be 1.3. Among 257 children with mental retardation of confirmed genetic origin B:G = 1.4, in 129 children with confirmed exogenous defects B:G = 1.04. The significant prevalence of boys over girls was characteristic of children with monogenic forms. The frequency of X-linked mental retardation in the total group, in all mentally retarded boys and in boys with genetic forms was 12.5 +/- 1.3%, 22.1 +/- 2.2% and 28.5 +/- 2.8%, respectively. The frequency of X-linked mental retardation was higher in boys with genetic forms of imbecility.     

The geneticist and the so-called socio cultural familial mental retardation

Five hundred children and adolescents affected by mild mental retardation were studied together with their families with regard to a number of psycho-social, medical and genetic factors. Statistical studies were performed with these data and showed that this apparently homogeneous population could in fact be divided into three subgroups. The first and by far the largest group (66%) was constituted by a clinically normal population but in whom adverse social and cultural factors were dominant. In the second subgroup (20%) the mental retardation was much more pronounced (IQ of 50----65) and the socio-cultural and socio-economic levels were particularly low. Finally, organic causes (prematurity, dystocic, labour, etc.) seemed to constitute the principal factor explaining the retardation observed in the third subgroup (14%). The second subgroup comprising of 50 children and their families, were observed more closely; in this group 20 cases of known genetic diseases were found.     

The effect of a traditional dance training program on dynamic balance of individuals with mental retardation

The purpose of this study was to evaluate the influence of a Greek traditional dance training program on the dynamic balance of individuals with mental retardation (MR). A total of 17 individuals participated in this study. Ten individuals with mild or moderate MR and 7 individuals with mild or moderate MR who studied in special schools were assigned to intervention (MR-I) and control (MR-C) groups, respectively. Pretraining and posttraining exercise tests were performed to determine the dynamic balance ability. Dynamic balance ability was measured by means of a balance deck (Lafayette, Lafayette, IN, USA) in 30-, 45-, and 60-second intervals. The MR-I group underwent a 16-week Greek traditional dance training program at a frequency of 3 times per week and for a duration of 45 minutes per season. Posttraining results showed that the individuals with MR in the MR-I group improved during treatment, from their baseline scores on dynamic balance measurements (30 seconds: p < 0.01, 45 seconds: p < 0.05, 60 seconds: p < 0.05). The MR-C group did not show any improvement between the 2 measurements. In conclusion, individuals with MR may be able to improve their dynamic balance when performing a systematic and well-designed Greek traditional dance training program.     

The social selection alternative to sexual selection

Social selection offers an alternative to sexual selection by reversing its logic. Social selection starts with offspring production and works back to mating, and starts with behavioural dynamics and works up to gene pool dynamics. In social selection, courtship can potentially be deduced as a negotiation, leading to an optimal allocation of tasks during offspring rearing. Ornaments facilitate this negotiation and also comprise 'admission tickets' to cliques. Mating pairs may form 'teams' based on the reciprocal sharing of pleasure. The parent-offspring relation can be managed by the parent considered as the owner of a 'family firm' whose product is offspring. The cooperation in reproductive social behaviour evolves as a mutual direct benefit through individual selection rather than as some form of altruism requiring kin or multi-level selection.     

Expression in fibroblast culture of the satellited-X chromosome associated with familial sex-linked mental retardation

Summary The satellited-X chromosome previously shown in lymphocyte culture to be associated with certain types of sex-linked mental retardation has, for the first time, been demonstrated in cultured skin fibroblasts and lymphocytes from two affected males and an obligate carrier female. These findings provide a basis for reliable diagnosis of female carriers and for the development of prenatal diagnosis.     

The clinico-genetic aspects of mental retardation related to the fragile-X chromosome]

This review deals with main problems of syndrome of X-fragile chromosome. The history of discovery and subsequent study of diseases as well as methods of examination, main clinical symptoms, methods of treatment and prophylaxis have been described. Some hypotheses, explaining complicated mechanism of fra-X syndrome inheritance are discussed. The recent achievements of molecular and genetic investigations of mental backwardness, associated with X-fragile chromosome are included in review.     

Lathosterolosis,a novel multiple-malformation/mental retardation syndrome due to deficiency of 3beta-hydroxysteroid-delta5-desaturase

We report the clinical, biochemical, and molecular characterization of a patient with a novel defect of cholesterol biosynthesis. This patient presented with a complex phenotype, including multiple congenital anomalies, mental retardation, and liver disease. In the patient's plasma and cells, we found increased levels of lathosterol. The biosynthesis of cholesterol in the patient's fibroblasts was defective, showing a block in the conversion of lathosterol into 7-dehydrocholesterol. The activity of 3beta-hydroxysteroid-Delta(5)-desaturase (SC5D), the enzyme involved in this reaction, was deficient in the patient's fibroblasts. Sequence analysis of the SC5D gene in the patient's DNA, showing the presence of two missense mutations (R29Q and G211D), confirmed that the patient is affected by a novel defect of cholesterol biosynthesis.     

The effect of age on the frequency of sperm chromosomal abnormalities in normal men.

It has been suggested that advanced paternal age (independent of maternal age) is associated with an increased incidence of trisomy. However, studies of human liveborn offspring and of data from prenatal diagnosis have yielded conflicting results. To investigate this possible paternal age effect, we have studied sperm chromosome complements from 30 normal men of proven fertility stratified by age, with five males in each of six age categories (20-24, 25-29, 30-34, 35-39, 40-44, and 45+ years). Sperm chromosome complements were visualized after penetration of golden-hamster oocytes. A minimum of 30 complements were analyzed for each male. The analysis was performed blindly, without knowledge of the donor's age. The mean frequency of sperm chromosomal abnormalities in the individual men was 10.4% with means of 4.7% for numerical abnormalities and 6.2% for structural abnormalities. There was no relationship between age and the frequency of numerical abnormalities in sperm. Since there was a significant difference between the frequency of hyperhaploid and hypohaploid complements, these two types of numerical abnormalities were analyzed separately. There was no correlation between the frequency of hypohaploid complements and age. There was a significant negative correlation between age and the frequency of hyperhaploid complements. For structural abnormalities, there was a highly significant positive correlation with age. Thus, our results do not support the hypothesis of an increased risk of trisomy with paternal age.     

The cytogenetics of 90 patients with idiopathic mental retardation/malformation syndromes and of 90 normal subjects

Summary A cytogenetic study, done on randomized coded slides, of 90 patients with idiopathic mental retardation and at least 3 other developmentally independent congenital anomalies and of 90 normal subjects is reported. Audiatorography, Q-banding and C-staining were used in the analysis of chromosomally abnormal cases. Eight patients were found to have chromosome abnormalities. Four had substantial chromosome aberrations that would be expected to cause abnormal phenotype. These were CD165 (46,18q-); CD25 (46,18q+) (partial trisomy of 10q); CD175 (46,4q+) and CD95 (46,mar22). In addition, 4 patients were found to have chromosomal anomalies that could not account for their conditions. Three of these were considered to have heterochromatic variants. Patient CD167 had an 9qh+ chromosome which had been inherited from her mother. Case CD137 had a No. 19 chromosome with additional centric heterochromatin. A similar chromosome was found in her mother, maternal grandmother and 2 of 3 half sibs. In patient CD125 a telocentric No. 13 was found. In addition, CD80 was shown to have an XYY constitution.In the normal subjects, no unbalanced chromosome rearrangements were found. Four persons, however, had minor chromosome anomalies. Three were considered to have heterochromatic variants. These were CD54 (46,22p+); CD149 (46,21p+) and CD19 (46,tel22). One normal subject (CD51) was found to be a balanced t(13q14q) carrier. The translocation chromosome had been inherited from his father.     

The effect of central serotonin administration on the neurogenic damage to the gastric mucosa due to chronic social stress in inbred mice]

A reiterated negative experience of intermale confrontations for 3 and 10 days resulted in aggravation of neurogenic ulceration of gastric mucosa in defeated males from all strains of mice under study, the number of mucosa erosions being 2-3-fold greater than in winners or control animals. Administration of serotonine into the lateral ventricles increased the number of erosions in intact mice of all genotypes. In experimental groups, a considerable diversity was found in respect to the effects of exogenous serotonine on the gastric mucosa. Following 10 days of the stress, both in winners and losers, a decrease of the gastric mucosa sensitivity to central serotonine was revealed.     

Angelman syndrome methylation screening of 15q11-q13 in institutionalized individuals with severe mental retardation

Among several genetic diseases that comprise mental retardation, Angelman syndrome (AS) has been extensively recognized and investigated. In the general population, the syndrome occurs in about 1 in 20,000 live births and its prevalence in severely mentally retarded individuals is 1.4%. These figures, however, may be an underestimate, because of the variable phenotype of AS. The main objective of this work was to investigate AS patients among a group of mentally retarded subjects, using the methylation pattern of the SNRPN gene, as determined by Southern blotting molecular analysis. The molecular investigation of 75 institutionalized individuals with severe to profound mental retardation resulted in the detection of 1 case with an abnormal methylation pattern of the SNRPN gene, corresponding to AS. The patient's phenotype was classified as atypical, without outbursts of inappropriate laughter or a happy disposition; the patient would not have been diagnosed in the usual screens for AS, which only select patients who demonstrate the typical clinical findings characteristic of the disease.     

The effect of single-nucleotide polymorphism marker selection on patterns of haplotype blocks and haplotype frequency estimates

The definition of haplotype blocks of single-nucleotide polymorphisms (SNPs) has been proposed so that the haplotypes can be used as markers in association studies and to efficiently describe human genetic variation. The International Haplotype Map (HapMap) project to construct a comprehensive catalog of haplotypic variation in humans is underway. However, a number of factors have already been shown to influence the definition of blocks, including the population studied and the sample SNP density. Here, we examine the effect that marker selection has on the definition of blocks and the pattern of haplotypes by using comparable but complementary SNP sets and a number of block definition methods in various genomic regions and populations that were provided by the Encyclopedia of DNA Elements (ENCODE) project. We find that the chosen SNP set has a profound effect on the block-covered sequence and block borders, even at high marker densities. Our results question the very concept of discrete haplotype blocks and the possibility of generalizing block findings from the HapMap project. We comparatively apply the block-free tagging-SNP approach and discuss both the haplotype approach and the tagging-SNP approach as means to efficiently catalog genetic variation.     

The effect of selection on genealogies

The coalescent process can describe the effects of selection at linked loci only if selection is so strong that genotype frequencies evolve deterministically. Here, we develop methods proposed by Kaplan, Darden, and Hudson to find the effects of weak selection. We show that the overall effect is given by an extension to Price's equation: the change in properties such as moments of coalescence times is equal to the covariance between those properties and the fitness of the sample of genes. The distribution of coalescence times differs substantially between allelic classes, even in the absence of selection. However, the average coalescence time between randomly chosen genes is insensitive to the current allele frequency and is affected significantly by purifying selection only if deleterious mutations are common and selection is strong (i.e., the product of population size and selection coefficient, Ns>3). Balancing selection increases mean coalescence times, but the effect becomes large only when mutation rates between allelic classes are low and when selection is extremely strong. Our analysis supports previous simulations that show that selection has surprisingly little effect on genealogies. Moreover, small fluctuations in allele frequency due to random drift can greatly reduce any such effects. This will make it difficult to detect the action of selection from neutral variation alone.